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Liver Failure_Paediatric v1.24 YKT6 Zornitza Stark Marked gene: YKT6 as ready
Liver Failure_Paediatric v1.24 YKT6 Zornitza Stark Gene: ykt6 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v1.24 YKT6 Zornitza Stark Classified gene: YKT6 as Amber List (moderate evidence)
Liver Failure_Paediatric v1.24 YKT6 Zornitza Stark Gene: ykt6 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v1.23 YKT6 Zornitza Stark gene: YKT6 was added
gene: YKT6 was added to Liver Failure_Paediatric. Sources: Literature
Mode of inheritance for gene: YKT6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YKT6 were set to 38522068
Phenotypes for gene: YKT6 were set to Syndromic disease, MONDO:0002254, YKT6-related
Review for gene: YKT6 was set to AMBER
Added comment: Two individuals homozygous for YKT6 [NM_006555.3:c.554A>G p.(Tyr185Cys)] exhibited normal prenatal course followed by failure to thrive, developmental delay and progressive liver disease. Haplotype analysis identified a shared homozygous region flanking the variant, suggesting a common ancestry. The third individual homozygous for YKT6 [NM_006555.3:c.191A>G p.(Tyr64Cys)] exhibited neurodevelopmental disorders and optic atrophy. Supportive functional data in Drosophila. Amber rating due to homozygous missense variants and founder effect in two of the families.
Sources: Literature
Liver Failure_Paediatric v1.22 MTM1 Zornitza Stark Marked gene: MTM1 as ready
Liver Failure_Paediatric v1.22 MTM1 Zornitza Stark Gene: mtm1 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v1.22 MTM1 Zornitza Stark Phenotypes for gene: MTM1 were changed from X-linked myotubular myopathy to Myopathy, centronuclear, X-linked, MIM# 310400
Liver Failure_Paediatric v1.21 MTM1 Zornitza Stark Classified gene: MTM1 as Amber List (moderate evidence)
Liver Failure_Paediatric v1.21 MTM1 Zornitza Stark Gene: mtm1 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v1.20 MTM1 Zornitza Stark reviewed gene: MTM1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Myopathy, centronuclear, X-linked, MIM# 310400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Liver Failure_Paediatric v1.20 MTM1 Rylee Peters changed review comment from: Functional studies using a zebrafish model of X-linked myotubular myopathy showed that loss-of-function mutations in the MTM1 gene led to severe liver abnormalities including impaired bile flux, structural abnormalities of the bile canaliculus, and improper endosome-mediated trafficking of canalicular transporters.
Sources: Literature; to: Functional studies using a zebrafish model of X-linked myotubular myopathy showed that loss-of-function mutations in the MTM1 gene led to severe liver abnormalities including impaired bile flux, structural abnormalities of the bile canaliculus, and improper endosome-mediated trafficking of canalicular transporters.
Sources: Literature
Liver Failure_Paediatric v1.20 MTM1 Rylee Peters edited their review of gene: MTM1: Changed rating: AMBER; Changed phenotypes: Myopathy, centronuclear, X-linked, MIM# 310400
Liver Failure_Paediatric v1.20 MTM1 Rylee Peters changed review comment from: Functional studies using a zebrafish model of X-linked myotubular myopathy showed that loss-of-function mutations in the MTM1 gene led to severe liver abnormalities including impaired bile flux, structural abnormalities of the bile canaliculus, and improper endosome-mediated trafficking of canalicular transporters.
Sources: Literature; to: Functional studies using a zebrafish model of X-linked myotubular myopathy showed that loss-of-function mutations in the MTM1 gene led to severe liver abnormalities including impaired bile flux, structural abnormalities of the bile canaliculus, and improper endosome-mediated trafficking of canalicular transporters.
Sources: Literature
Liver Failure_Paediatric v1.20 MTM1 Rylee Peters gene: MTM1 was added
gene: MTM1 was added to Liver Failure_Paediatric. Sources: Literature
Mode of inheritance for gene: MTM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MTM1 were set to PMID: 37490339
Phenotypes for gene: MTM1 were set to X-linked myotubular myopathy
Added comment: Functional studies using a zebrafish model of X-linked myotubular myopathy showed that loss-of-function mutations in the MTM1 gene led to severe liver abnormalities including impaired bile flux, structural abnormalities of the bile canaliculus, and improper endosome-mediated trafficking of canalicular transporters.
Sources: Literature
Liver Failure_Paediatric v1.20 Zornitza Stark HPO terms changed from to Liver failure, HP:0001399
List of related panels changed from to Liver failure; HP:0001399
Liver Failure_Paediatric v1.19 FAH Zornitza Stark Tag treatable tag was added to gene: FAH.
Liver Failure_Paediatric v1.19 GALT Zornitza Stark Tag treatable tag was added to gene: GALT.
Liver Failure_Paediatric v1.19 HADHB Zornitza Stark Tag treatable tag was added to gene: HADHB.
Liver Failure_Paediatric v1.19 HADHA Zornitza Stark Tag treatable tag was added to gene: HADHA.
Liver Failure_Paediatric v1.19 ACADM Zornitza Stark Tag treatable tag was added to gene: ACADM.
Liver Failure_Paediatric v1.19 LIPA Zornitza Stark Tag treatable tag was added to gene: LIPA.
Liver Failure_Paediatric v1.19 CPT2 Zornitza Stark Tag treatable tag was added to gene: CPT2.
Liver Failure_Paediatric v1.19 ALDOB Zornitza Stark Tag treatable tag was added to gene: ALDOB.
Liver Failure_Paediatric v1.19 AKR1D1 Zornitza Stark Tag treatable tag was added to gene: AKR1D1.
Liver Failure_Paediatric v1.19 FOCAD Zornitza Stark Phenotypes for gene: FOCAD were changed from Infantile liver failure, MONDO:0000023, FOCAD-related to Liver disease, severe congenital, MIM# 619991
Liver Failure_Paediatric v1.18 FOCAD Zornitza Stark edited their review of gene: FOCAD: Changed phenotypes: Liver disease, severe congenital, MIM# 619991
Liver Failure_Paediatric v1.18 FOCAD Zornitza Stark Marked gene: FOCAD as ready
Liver Failure_Paediatric v1.18 FOCAD Zornitza Stark Gene: focad has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.18 FOCAD Zornitza Stark Phenotypes for gene: FOCAD were changed from pediatric syndromic liver cirrhosis to Infantile liver failure, MONDO:0000023, FOCAD-related
Liver Failure_Paediatric v1.17 FOCAD Zornitza Stark Mode of pathogenicity for gene: FOCAD was changed from Other to None
Liver Failure_Paediatric v1.16 FOCAD Zornitza Stark Classified gene: FOCAD as Green List (high evidence)
Liver Failure_Paediatric v1.16 FOCAD Zornitza Stark Gene: focad has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.15 FOCAD Zornitza Stark reviewed gene: FOCAD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Infantile liver failure, MONDO:0000023, FOCAD-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Liver Failure_Paediatric v1.15 FOCAD Suliman Khan changed review comment from: Moreno Traspas et al 2022 reported 14 children from ten unrelated families with syndromic form of pediatric liver cirrhosis. Genome/exome sequencing analysis reveled biallelic variants in the FOCAD gene. Most of the mutations were nonsense, frameshift, or splice site alterations, predicted to result in a loss of function, but there were also 3 missense variants at highly conserved residues. Western blot analysis of dermal fibroblasts derived from 2 patients showed near absent FOCAD expression in cellular extracts. There were also decreased levels of the SKIC2 protein, suggesting that FOCAD may contribute to the stability of this RNA helicase (OMIM: 619991).
Sources: Literature; to: Moreno Traspas et al 2022 reported 14 children from ten unrelated families with syndromic form of pediatric liver cirrhosis. Genome/exome sequencing analysis reveled biallelic variants in the FOCAD gene. Most of the mutations were nonsense, frameshift, or splice site alterations, predicted to result in a loss of function, but there were also 3 missense variants at highly conserved residues. Western blot analysis of dermal fibroblasts derived from 2 patients showed near absent FOCAD expression in cellular extracts. There were also decreased levels of the SKIC2 protein, suggesting that FOCAD may contribute to the stability of RNA helicase (OMIM: 619991).
Sources: Literature, OMIM
Liver Failure_Paediatric v1.15 FOCAD Suliman Khan gene: FOCAD was added
gene: FOCAD was added to Liver Failure_Paediatric. Sources: Literature
Mode of inheritance for gene: FOCAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOCAD were set to PMID: 35864190
Phenotypes for gene: FOCAD were set to pediatric syndromic liver cirrhosis
Penetrance for gene: FOCAD were set to Complete
Mode of pathogenicity for gene: FOCAD was set to Other
Review for gene: FOCAD was set to GREEN
gene: FOCAD was marked as current diagnostic
Added comment: Moreno Traspas et al 2022 reported 14 children from ten unrelated families with syndromic form of pediatric liver cirrhosis. Genome/exome sequencing analysis reveled biallelic variants in the FOCAD gene. Most of the mutations were nonsense, frameshift, or splice site alterations, predicted to result in a loss of function, but there were also 3 missense variants at highly conserved residues. Western blot analysis of dermal fibroblasts derived from 2 patients showed near absent FOCAD expression in cellular extracts. There were also decreased levels of the SKIC2 protein, suggesting that FOCAD may contribute to the stability of this RNA helicase (OMIM: 619991).
Sources: Literature
Liver Failure_Paediatric v1.15 SKIV2L Zornitza Stark Marked gene: SKIV2L as ready
Liver Failure_Paediatric v1.15 SKIV2L Zornitza Stark Gene: skiv2l has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.15 SKIV2L Zornitza Stark Publications for gene: SKIV2L were set to PMID: 22444670, 33114497, 30397475, 29527791, 29484573
Liver Failure_Paediatric v1.14 TULP3 Zornitza Stark Marked gene: TULP3 as ready
Liver Failure_Paediatric v1.14 TULP3 Zornitza Stark Gene: tulp3 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.14 TULP3 Zornitza Stark Phenotypes for gene: TULP3 were changed from progressive degenerative liver fibrosis with variable fibrocystic kidney disease; hypertrophic cardiomyopathy MONDO:0005045 to Hepatorenocardiac degenerative fibrosis, MIM# 619902
Liver Failure_Paediatric v1.13 TULP3 Zornitza Stark reviewed gene: TULP3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hepatorenocardiac degenerative fibrosis, MIM# 619902; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Liver Failure_Paediatric v1.13 SKIV2L Chirag Patel Classified gene: SKIV2L as Green List (high evidence)
Liver Failure_Paediatric v1.13 SKIV2L Chirag Patel Gene: skiv2l has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.12 SKIV2L Chirag Patel gene: SKIV2L was added
gene: SKIV2L was added to Liver Failure_Paediatric. Sources: Literature
Mode of inheritance for gene: SKIV2L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SKIV2L were set to PMID: 22444670, 33114497, 30397475, 29527791, 29484573
Phenotypes for gene: SKIV2L were set to Trichohepatoenteric syndrome 2, MIM# 614602; Respiratory infections; IUGR; Facial dysmorphic features; Wooly hair; Early-onset intractable diarrhoea; Liver cirrhosis; Platelet abnormalities
Review for gene: SKIV2L was set to GREEN
gene: SKIV2L was marked as current diagnostic
Added comment: Numerous families reported.
Sources: Literature
Liver Failure_Paediatric v1.11 TULP3 Chirag Patel Classified gene: TULP3 as Green List (high evidence)
Liver Failure_Paediatric v1.11 TULP3 Chirag Patel Gene: tulp3 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.10 TULP3 Chirag Patel gene: TULP3 was added
gene: TULP3 was added to Liver Failure_Paediatric. Sources: Literature
Mode of inheritance for gene: TULP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TULP3 were set to PMID: 35397207
Phenotypes for gene: TULP3 were set to progressive degenerative liver fibrosis with variable fibrocystic kidney disease; hypertrophic cardiomyopathy MONDO:0005045
Review for gene: TULP3 was set to GREEN
gene: TULP3 was marked as current diagnostic
Added comment: 15 individuals from eight unrelated families with bi-allelic variants in TULP3 were detected. The affected individuals reported are mostly adults, in the 3rd through 7th decades of life, and presented with progressive degenerative liver fibrosis, then variable fibrocystic kidney disease and then hypertrophic cardiomyopathy. The human phenotype was recapitulated in adult zebrafish and confirmed disruption of critical ciliary cargo composition in several primary cell lines derived from affected individuals. Some G-P correlation with 2 x PTV leading to childhood disease (<10yrs), and 2 x missense variants leading to adult onset disease (>20yrs).
Sources: Literature
Liver Failure_Paediatric v1.9 MED12 Zornitza Stark Phenotypes for gene: MED12 were changed from Hardikar syndrome, OMIM #612726 to Hardikar syndrome, MIM# 301068
Liver Failure_Paediatric v1.8 MED12 Zornitza Stark reviewed gene: MED12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hardikar syndrome, MIM# 301068; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Liver Failure_Paediatric v1.8 BCS1L Zornitza Stark Phenotypes for gene: BCS1L were changed from GRACILE syndrome, MIM# 603358; Mitochondrial complex III deficiency, nuclear type 1 , MIM#124000 to GRACILE syndrome, MIM# 603358; Mitochondrial complex III deficiency, nuclear type 1 , MIM#112400
Liver Failure_Paediatric v1.7 BCS1L Zornitza Stark edited their review of gene: BCS1L: Changed phenotypes: GRACILE syndrome, MIM# 603358, Mitochondrial complex III deficiency, nuclear type 1 , MIM#112400
Liver Failure_Paediatric v1.7 SLC37A4 Sue White Marked gene: SLC37A4 as ready
Liver Failure_Paediatric v1.7 SLC37A4 Sue White Gene: slc37a4 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.7 SLC37A4 Sue White Classified gene: SLC37A4 as Green List (high evidence)
Liver Failure_Paediatric v1.7 SLC37A4 Sue White Gene: slc37a4 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.6 SLC37A4 Paul De Fazio edited their review of gene: SLC37A4: Changed phenotypes: Congenital disorder of glycosylation, liver dysfunction, coagulation deficiency
Liver Failure_Paediatric v1.6 SLC37A4 Paul De Fazio gene: SLC37A4 was added
gene: SLC37A4 was added to Liver Failure_Paediatric. Sources: Literature
Mode of inheritance for gene: SLC37A4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SLC37A4 were set to 33964207
Phenotypes for gene: SLC37A4 were set to Congenital disorder of glycosylation
Review for gene: SLC37A4 was set to GREEN
gene: SLC37A4 was marked as current diagnostic
Added comment: 7 patients from 4 families, additional to the two reported previously, described with the same recurrent c.1267C>T (p.R423*) variant with liver dysfunction multifactorial coagulation deficiency and cardiac issues. Serum samples from affected individuals showed profound accumulation of both high mannose and hybrid type N-glycans. Hepatoma cell-line studies support the pathogenicity of the variant.

Some patients diagnosed in adulthood but most in childhood.
Sources: Literature
Liver Failure_Paediatric v1.6 MED12 Zornitza Stark Marked gene: MED12 as ready
Liver Failure_Paediatric v1.6 MED12 Zornitza Stark Gene: med12 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.6 MED12 Chirag Patel Classified gene: MED12 as Green List (high evidence)
Liver Failure_Paediatric v1.6 MED12 Chirag Patel Gene: med12 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.5 MED12 Chirag Patel gene: MED12 was added
gene: MED12 was added to Liver Failure_Paediatric. Sources: Literature
Mode of inheritance for gene: MED12 was set to Other
Publications for gene: MED12 were set to PMID: 33244166
Phenotypes for gene: MED12 were set to Hardikar syndrome, OMIM #612726
Review for gene: MED12 was set to GREEN
Added comment: 7 female individuals (2 previously reported and 5 unpublished) reported with a clinical diagnosis of Hardikar syndrome (rare multiple congenital anomaly syndrome characterized by facial clefting, pigmentary retinopathy, biliary anomalies, hydronephrosis, and intestinal malrotation, but normal cognition).

Exome sequencing identified de novo pathogenic nonsense and frameshift variants in MED12 in all 7 individuals. Evidence of extremely skewed XCI in all patients with informative testing. No functional assays.

Note: pathogenic missense variants in MED12 associated with Opitz-Kaveggia syndrome, Lujan syndrome, Ohdo syndrome, and nonsyndromic intellectual disability, primarily in males
Sources: Literature
Liver Failure_Paediatric v1.4 PHKG2 Zornitza Stark Marked gene: PHKG2 as ready
Liver Failure_Paediatric v1.4 PHKG2 Zornitza Stark Gene: phkg2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.4 PHKG2 Zornitza Stark Classified gene: PHKG2 as Green List (high evidence)
Liver Failure_Paediatric v1.4 PHKG2 Zornitza Stark Gene: phkg2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.3 PHKG2 Zornitza Stark gene: PHKG2 was added
gene: PHKG2 was added to Liver Failure_Paediatric. Sources: Expert Review
Mode of inheritance for gene: PHKG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHKG2 were set to 8896567; 9384616; 10905889
Phenotypes for gene: PHKG2 were set to Glycogen storage disease IXc, MIM# 613027
Review for gene: PHKG2 was set to GREEN
Added comment: Glycogen storage disease IXc is characterized by onset in childhood of hepatomegaly, hypotonia, growth retardation in childhood, and liver dysfunction. These symptoms improve with age in most cases; however, some patients may develop hepatic fibrosis or cirrhosis.
Sources: Expert Review
Liver Failure_Paediatric v1.2 PYGL Zornitza Stark Marked gene: PYGL as ready
Liver Failure_Paediatric v1.2 PYGL Zornitza Stark Gene: pygl has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.2 PYGL Zornitza Stark Classified gene: PYGL as Green List (high evidence)
Liver Failure_Paediatric v1.2 PYGL Zornitza Stark Gene: pygl has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.1 PYGL Zornitza Stark gene: PYGL was added
gene: PYGL was added to Liver Failure_Paediatric. Sources: Literature
Mode of inheritance for gene: PYGL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYGL were set to 32892177
Phenotypes for gene: PYGL were set to Glycogen storage disease VI, MIM# 232700
Review for gene: PYGL was set to GREEN
Added comment: Progression to cirrhosis reported.
Sources: Literature
Liver Failure_Paediatric v1.0 Zornitza Stark promoted panel to version 1.0
Liver Failure_Paediatric v0.114 NOTCH2 Zornitza Stark Marked gene: NOTCH2 as ready
Liver Failure_Paediatric v0.114 NOTCH2 Zornitza Stark Gene: notch2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.114 NOTCH2 Zornitza Stark Classified gene: NOTCH2 as Green List (high evidence)
Liver Failure_Paediatric v0.114 NOTCH2 Zornitza Stark Gene: notch2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.113 NOTCH2 Zornitza Stark gene: NOTCH2 was added
gene: NOTCH2 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: NOTCH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NOTCH2 were set to Alagille syndrome 2, MIM# 610205
Review for gene: NOTCH2 was set to GREEN
Added comment: Well established gene-disease association.
Sources: Expert list
Liver Failure_Paediatric v0.112 ABCB4 Zornitza Stark Marked gene: ABCB4 as ready
Liver Failure_Paediatric v0.112 ABCB4 Zornitza Stark Gene: abcb4 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.112 ABCB4 Zornitza Stark Classified gene: ABCB4 as Green List (high evidence)
Liver Failure_Paediatric v0.112 ABCB4 Zornitza Stark Gene: abcb4 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.111 ABCB4 Zornitza Stark gene: ABCB4 was added
gene: ABCB4 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ABCB4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCB4 were set to 17726488
Phenotypes for gene: ABCB4 were set to Cholestasis, progressive familial intrahepatic 3, MIM# 602347
Review for gene: ABCB4 was set to GREEN
Added comment: Well established gene disease association.
Sources: Expert list
Liver Failure_Paediatric v0.110 ABCB11 Zornitza Stark Marked gene: ABCB11 as ready
Liver Failure_Paediatric v0.110 ABCB11 Zornitza Stark Gene: abcb11 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.110 ABCB11 Zornitza Stark Classified gene: ABCB11 as Green List (high evidence)
Liver Failure_Paediatric v0.110 ABCB11 Zornitza Stark Gene: abcb11 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.109 ABCB11 Zornitza Stark gene: ABCB11 was added
gene: ABCB11 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ABCB11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCB11 were set to 9806540
Phenotypes for gene: ABCB11 were set to Cholestasis, progressive familial intrahepatic 2, MIM# 601847
Review for gene: ABCB11 was set to GREEN
Added comment: Well established gene-disease association.
Sources: Expert list
Liver Failure_Paediatric v0.108 ATP8B1 Zornitza Stark Marked gene: ATP8B1 as ready
Liver Failure_Paediatric v0.108 ATP8B1 Zornitza Stark Gene: atp8b1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.108 ATP8B1 Zornitza Stark Classified gene: ATP8B1 as Green List (high evidence)
Liver Failure_Paediatric v0.108 ATP8B1 Zornitza Stark Gene: atp8b1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.107 ATP8B1 Zornitza Stark gene: ATP8B1 was added
gene: ATP8B1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ATP8B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP8B1 were set to 15239083
Phenotypes for gene: ATP8B1 were set to Cholestasis, progressive familial intrahepatic 1, MIM# 211600
Review for gene: ATP8B1 was set to GREEN
Added comment: Well established gene-disease association, early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver failure.
Sources: Expert list
Liver Failure_Paediatric v0.106 CPT2 Zornitza Stark Marked gene: CPT2 as ready
Liver Failure_Paediatric v0.106 CPT2 Zornitza Stark Gene: cpt2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.106 CPT2 Zornitza Stark Classified gene: CPT2 as Green List (high evidence)
Liver Failure_Paediatric v0.106 CPT2 Zornitza Stark Gene: cpt2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.105 CPT2 Zornitza Stark gene: CPT2 was added
gene: CPT2 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: CPT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPT2 were set to 8651281; 1528846; 12410208
Phenotypes for gene: CPT2 were set to CPT II deficiency, infantile, MIM# 600649
Review for gene: CPT2 was set to GREEN
Added comment: The infantile form usually presents between 6 and 24 months of age with recurrent attacks of hypoketotic hypoglycemia causing loss of consciousness and seizures, liver failure, and transient hepatomegaly. Some children also have heart involvement with cardiomyopathy and arrhythmia. Episodes are triggered by infections, fever, or fasting.
Sources: Expert list
Liver Failure_Paediatric v0.104 CYP7B1 Zornitza Stark Marked gene: CYP7B1 as ready
Liver Failure_Paediatric v0.104 CYP7B1 Zornitza Stark Gene: cyp7b1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.104 CYP7B1 Zornitza Stark Classified gene: CYP7B1 as Green List (high evidence)
Liver Failure_Paediatric v0.104 CYP7B1 Zornitza Stark Gene: cyp7b1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.103 CYP7B1 Zornitza Stark gene: CYP7B1 was added
gene: CYP7B1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: CYP7B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP7B1 were set to 9802883; 31337596; 21567895; 24658845
Phenotypes for gene: CYP7B1 were set to Bile acid synthesis defect, congenital, 3, MIM# 613812
Review for gene: CYP7B1 was set to GREEN
Added comment: At least 4 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.102 IARS Zornitza Stark Marked gene: IARS as ready
Liver Failure_Paediatric v0.102 IARS Zornitza Stark Gene: iars has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.102 IARS Zornitza Stark Classified gene: IARS as Green List (high evidence)
Liver Failure_Paediatric v0.102 IARS Zornitza Stark Gene: iars has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.101 IARS Zornitza Stark gene: IARS was added
gene: IARS was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: IARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IARS were set to 27426735; 27891590
Phenotypes for gene: IARS were set to Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, MIM# 617093
Review for gene: IARS was set to GREEN
Added comment: GRIDHH is an autosomal recessive multisystem disorder characterized by poor overall growth, impaired intellectual development, hypotonia, and variable liver dysfunction. Four unrelated families reported and a zebrafish model.
Sources: Expert list
Liver Failure_Paediatric v0.100 TTC37 Zornitza Stark Marked gene: TTC37 as ready
Liver Failure_Paediatric v0.100 TTC37 Zornitza Stark Gene: ttc37 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.100 TTC37 Zornitza Stark Classified gene: TTC37 as Green List (high evidence)
Liver Failure_Paediatric v0.100 TTC37 Zornitza Stark Gene: ttc37 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.99 TTC37 Zornitza Stark gene: TTC37 was added
gene: TTC37 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: TTC37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC37 were set to 17318842; 20176027
Phenotypes for gene: TTC37 were set to Trichohepatoenteric syndrome 1, MIM# 222470
Review for gene: TTC37 was set to GREEN
Added comment: Clinical features include intrauterine growth retardation, woolly hair, facial dysmorphism, intractable diarrhoea in infancy requiring total parenteral nutrition, and immunodepression. Hepatic involvement contributes to the poor prognosis of affected patients, cirrhosis reported.

More than 20 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.98 HSD3B7 Zornitza Stark Marked gene: HSD3B7 as ready
Liver Failure_Paediatric v0.98 HSD3B7 Zornitza Stark Gene: hsd3b7 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.98 HSD3B7 Zornitza Stark Classified gene: HSD3B7 as Green List (high evidence)
Liver Failure_Paediatric v0.98 HSD3B7 Zornitza Stark Gene: hsd3b7 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.97 HSD3B7 Zornitza Stark gene: HSD3B7 was added
gene: HSD3B7 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: HSD3B7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSD3B7 were set to 12679481; 11067870
Phenotypes for gene: HSD3B7 were set to Bile acid synthesis defect, congenital, 1, MIM# 607765
Review for gene: HSD3B7 was set to GREEN
Added comment: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive metabolic disorder characterized by poor growth, intrahepatic cholestasis, and increased serum citrulline. Most individuals show spontaneous improvement by 1 year of age. However, some may have a progressive course with continued failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and some may develop chronic or fatal liver disease.

More than 10 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.96 CCDC115 Zornitza Stark Marked gene: CCDC115 as ready
Liver Failure_Paediatric v0.96 CCDC115 Zornitza Stark Gene: ccdc115 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.96 CCDC115 Zornitza Stark Classified gene: CCDC115 as Green List (high evidence)
Liver Failure_Paediatric v0.96 CCDC115 Zornitza Stark Gene: ccdc115 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.95 CCDC115 Zornitza Stark gene: CCDC115 was added
gene: CCDC115 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: CCDC115 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC115 were set to 26833332; 29759592
Phenotypes for gene: CCDC115 were set to Congenital disorder of glycosylation, type IIo, MIM# 616828
Review for gene: CCDC115 was set to GREEN
Added comment: Autosomal recessive metabolic disorder characterized by infantile onset of progressive liver failure, hypotonia, and delayed psychomotor development. Laboratory abnormalities include elevated liver enzymes, coagulation factor deficiencies, hypercholesterolemia, and low ceruloplasmin. Serum isoelectric focusing of proteins shows a combined defect of N- and O-glycosylation, suggestive of a Golgi defect.
Sources: Expert list
Liver Failure_Paediatric v0.94 AMACR Zornitza Stark changed review comment from: Intrahepatic cholestasis and liver failure in infancy.
Sources: Expert list; to: Intrahepatic cholestasis and liver failure in infancy, at least three families and mouse model.
Sources: Expert list
Liver Failure_Paediatric v0.94 AMACR Zornitza Stark Marked gene: AMACR as ready
Liver Failure_Paediatric v0.94 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.94 AMACR Zornitza Stark Classified gene: AMACR as Green List (high evidence)
Liver Failure_Paediatric v0.94 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.93 AMACR Zornitza Stark gene: AMACR was added
gene: AMACR was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: AMACR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMACR were set to 31951345; 24735479; 12512044; 10655068
Phenotypes for gene: AMACR were set to Bile acid synthesis defect, congenital, 4, MIM# 214950
Review for gene: AMACR was set to GREEN
Added comment: Intrahepatic cholestasis and liver failure in infancy.
Sources: Expert list
Liver Failure_Paediatric v0.92 HADHB Zornitza Stark Marked gene: HADHB as ready
Liver Failure_Paediatric v0.92 HADHB Zornitza Stark Gene: hadhb has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.92 HADHB Zornitza Stark Classified gene: HADHB as Green List (high evidence)
Liver Failure_Paediatric v0.92 HADHB Zornitza Stark Gene: hadhb has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.91 HADHB Zornitza Stark gene: HADHB was added
gene: HADHB was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: HADHB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HADHB were set to Trifunctional protein deficiency, MIM# 609015
Review for gene: HADHB was set to GREEN
Added comment: Trifunctional protein deficiency can be classified into 3 main clinical phenotypes: neonatal onset of a severe, lethal condition resulting in sudden unexplained infant death, infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal myopathy.
Sources: Expert list
Liver Failure_Paediatric v0.90 HADHA Zornitza Stark Marked gene: HADHA as ready
Liver Failure_Paediatric v0.90 HADHA Zornitza Stark Gene: hadha has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.90 HADHA Zornitza Stark Classified gene: HADHA as Green List (high evidence)
Liver Failure_Paediatric v0.90 HADHA Zornitza Stark Gene: hadha has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.89 HADHA Zornitza Stark gene: HADHA was added
gene: HADHA was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: HADHA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HADHA were set to Mitochondrial trifunctional protein deficiency, MIM# 609015
Review for gene: HADHA was set to GREEN
Added comment: Trifunctional protein deficiency can be classified into 3 main clinical phenotypes: neonatal onset of a severe, lethal condition resulting in sudden unexplained infant death, infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal myopathy.
Sources: Expert list
Liver Failure_Paediatric v0.88 GBE1 Zornitza Stark Marked gene: GBE1 as ready
Liver Failure_Paediatric v0.88 GBE1 Zornitza Stark Gene: gbe1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.88 GBE1 Zornitza Stark Classified gene: GBE1 as Green List (high evidence)
Liver Failure_Paediatric v0.88 GBE1 Zornitza Stark Gene: gbe1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.87 GBE1 Zornitza Stark gene: GBE1 was added
gene: GBE1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: GBE1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GBE1 were set to Glycogen storage disease IV, MIM# 232500
Review for gene: GBE1 was set to GREEN
Added comment: Typically presents with liver disease in childhood, progressing to cirrhosis.
Sources: Expert list
Liver Failure_Paediatric v0.86 MRM2 Zornitza Stark Marked gene: MRM2 as ready
Liver Failure_Paediatric v0.86 MRM2 Zornitza Stark Gene: mrm2 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.86 MRM2 Zornitza Stark Classified gene: MRM2 as Amber List (moderate evidence)
Liver Failure_Paediatric v0.86 MRM2 Zornitza Stark Gene: mrm2 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.85 MRM2 Zornitza Stark gene: MRM2 was added
gene: MRM2 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: MRM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRM2 were set to 28973171
Phenotypes for gene: MRM2 were set to Mitochondrial DNA depletion syndrome 17, MIM# 618567
Review for gene: MRM2 was set to AMBER
Added comment: Single individual reported plus functional data. MRM2 encodes an enzyme responsible for 2'-O-methyl modification at position U1369 in the human mitochondrial 16S rRNA.

Recurrent episodes of liver failure were part of the clinical course.
Sources: Expert list
Liver Failure_Paediatric v0.84 ALMS1 Zornitza Stark Marked gene: ALMS1 as ready
Liver Failure_Paediatric v0.84 ALMS1 Zornitza Stark Gene: alms1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.84 ALMS1 Zornitza Stark Classified gene: ALMS1 as Green List (high evidence)
Liver Failure_Paediatric v0.84 ALMS1 Zornitza Stark Gene: alms1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.83 ALMS1 Zornitza Stark gene: ALMS1 was added
gene: ALMS1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ALMS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALMS1 were set to 25296579
Phenotypes for gene: ALMS1 were set to Alstrom syndrome, MIM# 203800
Review for gene: ALMS1 was set to GREEN
Added comment: Autosomal recessive disorder characterized by progressive cone-rod dystrophy leading to blindness, sensorineural hearing loss, childhood obesity associated with hyperinsulinemia, and type 2 diabetes mellitus. Dilated cardiomyopathy occurs in approximately 70% of patients during infancy or adolescence. Renal failure, pulmonary, hepatic, and urologic dysfunction are often observed, and systemic fibrosis develops with age.

Chronic active hepatitis, hepatomegaly, steatosis, and cirrhosis all reported.
Sources: Expert list
Liver Failure_Paediatric v0.82 CYC1 Zornitza Stark Marked gene: CYC1 as ready
Liver Failure_Paediatric v0.82 CYC1 Zornitza Stark Gene: cyc1 has been classified as Red List (Low Evidence).
Liver Failure_Paediatric v0.82 CYC1 Zornitza Stark gene: CYC1 was added
gene: CYC1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: CYC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYC1 were set to 23910460
Phenotypes for gene: CYC1 were set to Mitochondrial complex III deficiency, nuclear type 6, MIM# 615453
Review for gene: CYC1 was set to RED
Added comment: Two families reported, of these episodes of acute liver failure reported in one proband.
Sources: Expert list
Liver Failure_Paediatric v0.81 TJP2 Zornitza Stark Marked gene: TJP2 as ready
Liver Failure_Paediatric v0.81 TJP2 Zornitza Stark Gene: tjp2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.81 TJP2 Zornitza Stark Classified gene: TJP2 as Green List (high evidence)
Liver Failure_Paediatric v0.81 TJP2 Zornitza Stark Gene: tjp2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.80 TJP2 Zornitza Stark gene: TJP2 was added
gene: TJP2 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: TJP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TJP2 were set to 24614073; 25921221; 31696999
Phenotypes for gene: TJP2 were set to Cholestasis, progressive familial intrahepatic 4, MIM# 615878
Review for gene: TJP2 was set to GREEN
Added comment: Early childhood onset of severe progressive liver disease. At leat 20 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.79 ATP6AP2 Zornitza Stark Marked gene: ATP6AP2 as ready
Liver Failure_Paediatric v0.79 ATP6AP2 Zornitza Stark Gene: atp6ap2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.79 ATP6AP2 Zornitza Stark Classified gene: ATP6AP2 as Green List (high evidence)
Liver Failure_Paediatric v0.79 ATP6AP2 Zornitza Stark Gene: atp6ap2 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.78 ATP6AP2 Zornitza Stark edited their review of gene: ATP6AP2: Changed rating: GREEN; Changed phenotypes: Congenital disorder of glycosylation, type IIr, MIM# 301045
Liver Failure_Paediatric v0.78 ATP6AP2 Zornitza Stark gene: ATP6AP2 was added
gene: ATP6AP2 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ATP6AP2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ATP6AP2 were set to 29127204; 29388887
Phenotypes for gene: ATP6AP2 were set to Congenital disorder of glycosylation, type IIr, MIM# 301045
Added comment: Congenital disorder of glycosylation type 2R (CDG2R) is an X-linked recessive disorder characterized by infantile onset of liver failure, recurrent infections due to hypogammaglobulinemia, and cutis laxa. Some individuals may also have mild intellectual impairment and dysmorphic features. Laboratory studies showed defective glycosylation of serum transferrin in a type 2 pattern.

Two unrelated families and functional data support gene-disease association.
Sources: Expert list
Liver Failure_Paediatric v0.77 STN1 Zornitza Stark Marked gene: STN1 as ready
Liver Failure_Paediatric v0.77 STN1 Zornitza Stark Gene: stn1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.77 STN1 Zornitza Stark Classified gene: STN1 as Green List (high evidence)
Liver Failure_Paediatric v0.77 STN1 Zornitza Stark Gene: stn1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.76 STN1 Zornitza Stark gene: STN1 was added
gene: STN1 was added to Liver Failure_Paediatric. Sources: Literature
Mode of inheritance for gene: STN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STN1 were set to 27432940; 32627942
Phenotypes for gene: STN1 were set to Cerebroretinal microangiopathy with calcification and cysts 2, MIM#617341
Review for gene: STN1 was set to GREEN
Added comment: Three unrelated families described with a multisystem disorder characterized by premature aging, pancytopaenia, hypocellular bone marrow, osteopenia, liver fibrosis, and vascular telangiectasia resulting in gastrointestinal bleeding, as well as intracranial calcifications and leukodystrophy, resulting in spasticity, ataxia, or dystonia.
Sources: Literature
Liver Failure_Paediatric v0.75 BCS1L Zornitza Stark Marked gene: BCS1L as ready
Liver Failure_Paediatric v0.75 BCS1L Zornitza Stark Gene: bcs1l has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.75 BCS1L Zornitza Stark Classified gene: BCS1L as Green List (high evidence)
Liver Failure_Paediatric v0.75 BCS1L Zornitza Stark Gene: bcs1l has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.74 BCS1L Zornitza Stark gene: BCS1L was added
gene: BCS1L was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: BCS1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BCS1L were set to 12910490; 12215968; 21274865
Phenotypes for gene: BCS1L were set to GRACILE syndrome, MIM# 603358; Mitochondrial complex III deficiency, nuclear type 1 , MIM#124000
Review for gene: BCS1L was set to GREEN
Added comment: The two phenotypes pertinent to this panel are a Leigh-like syndrome; and growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis and early death (GRACILE syndrome). Mitochondrial hepatopathy.
Sources: Expert list
Liver Failure_Paediatric v0.73 POLG2 Zornitza Stark Marked gene: POLG2 as ready
Liver Failure_Paediatric v0.73 POLG2 Zornitza Stark Gene: polg2 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.73 POLG2 Zornitza Stark Classified gene: POLG2 as Amber List (moderate evidence)
Liver Failure_Paediatric v0.73 POLG2 Zornitza Stark Gene: polg2 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.72 POLG2 Zornitza Stark gene: POLG2 was added
gene: POLG2 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: POLG2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POLG2 were set to 27592148; 30157269; 21555342
Phenotypes for gene: POLG2 were set to Mitochondrial DNA depletion syndrome 16 (hepatic type), MIM# 618528; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, MIM# 4 610131
Review for gene: POLG2 was set to AMBER
Added comment: Single family reported with bi-allelic variants in POLG2 and severe neonatal hepatic failure, some functional data to support variant pathogenicity. Note mono-allelic variants in this gene are associated with PEO phenotype, but onset and severity are highly variable including reports of childhood manifestations with liver dysfunction.
Sources: Expert list
Liver Failure_Paediatric v0.71 SH2D1A Zornitza Stark Marked gene: SH2D1A as ready
Liver Failure_Paediatric v0.71 SH2D1A Zornitza Stark Gene: sh2d1a has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.71 SH2D1A Zornitza Stark Classified gene: SH2D1A as Green List (high evidence)
Liver Failure_Paediatric v0.71 SH2D1A Zornitza Stark Gene: sh2d1a has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.70 SH2D1A Zornitza Stark gene: SH2D1A was added
gene: SH2D1A was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: SH2D1A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SH2D1A were set to 6306053; 9771704
Phenotypes for gene: SH2D1A were set to Lymphoproliferative syndrome, X-linked, 1, MIM# 308240
Review for gene: SH2D1A was set to GREEN
Added comment: A primary immunodeficiency characterized by severe immune dysregulation often after viral infection, typically with Epstein-Barr virus (EBV). It is a complex phenotype manifest as severe or fatal mononucleosis, acquired hypogammaglobulinema, hemophagocytic lymphohistiocytosis (HLH), and/or malignant lymphoma. Other features may include aplastic anemia, red cell aplasia, and lymphomatoid granulomatosis. Liver dysfunction, hepatic necrosis and liver failure reported.
Sources: Expert list
Liver Failure_Paediatric v0.69 TKFC Zornitza Stark Marked gene: TKFC as ready
Liver Failure_Paediatric v0.69 TKFC Zornitza Stark Gene: tkfc has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.69 TKFC Zornitza Stark Classified gene: TKFC as Amber List (moderate evidence)
Liver Failure_Paediatric v0.69 TKFC Zornitza Stark Gene: tkfc has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.68 TKFC Zornitza Stark gene: TKFC was added
gene: TKFC was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: TKFC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TKFC were set to 32004446
Phenotypes for gene: TKFC were set to Triokinase and FMN cyclase deficiency syndrome, MIM#618805; Developmental delay; cataracts; liver dysfunction
Review for gene: TKFC was set to AMBER
Added comment: Two unrelated families reported. Liver dysfunction, including liver failure in one.
Sources: Expert list
Liver Failure_Paediatric v0.67 ATP6AP1 Zornitza Stark Marked gene: ATP6AP1 as ready
Liver Failure_Paediatric v0.67 ATP6AP1 Zornitza Stark Gene: atp6ap1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.67 ATP6AP1 Zornitza Stark Classified gene: ATP6AP1 as Green List (high evidence)
Liver Failure_Paediatric v0.67 ATP6AP1 Zornitza Stark Gene: atp6ap1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.66 ATP6AP1 Zornitza Stark gene: ATP6AP1 was added
gene: ATP6AP1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ATP6AP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ATP6AP1 were set to 27231034; 32216104; 32058063; 29192153
Phenotypes for gene: ATP6AP1 were set to Immunodeficiency 47, MIM# 300972
Review for gene: ATP6AP1 was set to GREEN
Added comment: X-linked recessive complex syndrome characterized by liver dysfunction, recurrent bacterial infections, hypogammaglobulinemia, and defective glycosylation of serum proteins. Liver failure reported.
Sources: Expert list
Liver Failure_Paediatric v0.65 IL18BP Zornitza Stark Marked gene: IL18BP as ready
Liver Failure_Paediatric v0.65 IL18BP Zornitza Stark Gene: il18bp has been classified as Red List (Low Evidence).
Liver Failure_Paediatric v0.65 IL18BP Zornitza Stark gene: IL18BP was added
gene: IL18BP was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: IL18BP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL18BP were set to 31213488
Phenotypes for gene: IL18BP were set to {?Hepatitis, fulminant viral, susceptibility to} 618549
Review for gene: IL18BP was set to RED
Added comment: Single individual reported with homozygous 40bp deletion in this gene and fulminant Hep A hepatitis.
Sources: Expert list
Liver Failure_Paediatric v0.64 TFAM Zornitza Stark Marked gene: TFAM as ready
Liver Failure_Paediatric v0.64 TFAM Zornitza Stark Gene: tfam has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.64 TFAM Zornitza Stark Classified gene: TFAM as Amber List (moderate evidence)
Liver Failure_Paediatric v0.64 TFAM Zornitza Stark Gene: tfam has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.63 TFAM Zornitza Stark gene: TFAM was added
gene: TFAM was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: TFAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TFAM were set to 27448789; 29021295; 9500544
Phenotypes for gene: TFAM were set to Mitochondrial DNA depletion syndrome 15 (hepatocerebral type) MIM#617156
Review for gene: TFAM was set to AMBER
Added comment: Two sibs from one consanguineous family presenting with severe progressive liver disease and segregating a homozygous variant. Tfam knockout mouse has a mitochondrial cardiomyopathy phenotype and severe mtDNA depletion with abolished oxidative phosphorylation.
Sources: Expert list
Liver Failure_Paediatric v0.62 COQ2 Zornitza Stark Marked gene: COQ2 as ready
Liver Failure_Paediatric v0.62 COQ2 Zornitza Stark Gene: coq2 has been classified as Red List (Low Evidence).
Liver Failure_Paediatric v0.62 COQ2 Zornitza Stark gene: COQ2 was added
gene: COQ2 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: COQ2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ2 were set to 17332895
Phenotypes for gene: COQ2 were set to Coenzyme Q10 deficiency, primary, 1, MIM#607426
Review for gene: COQ2 was set to RED
Added comment: Manifestations of this disorder are principally encephalomyopathic and renal, however at least one report of liver failure.
Sources: Expert list
Liver Failure_Paediatric v0.61 SERAC1 Zornitza Stark Marked gene: SERAC1 as ready
Liver Failure_Paediatric v0.61 SERAC1 Zornitza Stark Gene: serac1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.61 SERAC1 Zornitza Stark Classified gene: SERAC1 as Green List (high evidence)
Liver Failure_Paediatric v0.61 SERAC1 Zornitza Stark Gene: serac1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.60 SERAC1 Zornitza Stark gene: SERAC1 was added
gene: SERAC1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: SERAC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERAC1 were set to 29205472
Phenotypes for gene: SERAC1 were set to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, MIM# 614739
Review for gene: SERAC1 was set to GREEN
Added comment: Autosomal recessive disorder characterized by childhood onset of delayed psychomotor development or psychomotor regression, sensorineural deafness, spasticity or dystonia, and increased excretion of 3-methylglutaconic acid. About 50% develop severe, but transient, liver dysfunction and/or signs of liver failure, in the neonatal period or during the first year of life.

More than 50 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.59 ABCD3 Zornitza Stark Marked gene: ABCD3 as ready
Liver Failure_Paediatric v0.59 ABCD3 Zornitza Stark Gene: abcd3 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.59 ABCD3 Zornitza Stark Classified gene: ABCD3 as Amber List (moderate evidence)
Liver Failure_Paediatric v0.59 ABCD3 Zornitza Stark Gene: abcd3 has been classified as Amber List (Moderate Evidence).
Liver Failure_Paediatric v0.58 ABCD3 Zornitza Stark gene: ABCD3 was added
gene: ABCD3 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ABCD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCD3 were set to 25168382
Phenotypes for gene: ABCD3 were set to Bile acid synthesis defect, congenital, 5 (MIM#616278)
Review for gene: ABCD3 was set to AMBER
Added comment: Single individual reported in 2015. Evidence of a bile acid biosynthesis defect in both the affected individual and knock out mice.
Sources: Expert list
Liver Failure_Paediatric v0.57 GFM1 Zornitza Stark Marked gene: GFM1 as ready
Liver Failure_Paediatric v0.57 GFM1 Zornitza Stark Gene: gfm1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.57 GFM1 Zornitza Stark Classified gene: GFM1 as Green List (high evidence)
Liver Failure_Paediatric v0.57 GFM1 Zornitza Stark Gene: gfm1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.56 GFM1 Zornitza Stark gene: GFM1 was added
gene: GFM1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: GFM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GFM1 were set to 31680380; 23430926
Phenotypes for gene: GFM1 were set to Combined oxidative phosphorylation deficiency 1, MIM# 609060
Review for gene: GFM1 was set to GREEN
Added comment: Multi-system mitochondrial disorder, predominantly neurological features with or without hepatic involvement. Liver failure reported.
Sources: Expert list
Liver Failure_Paediatric v0.55 NR1H4 Zornitza Stark Marked gene: NR1H4 as ready
Liver Failure_Paediatric v0.55 NR1H4 Zornitza Stark Gene: nr1h4 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.55 NR1H4 Zornitza Stark Classified gene: NR1H4 as Green List (high evidence)
Liver Failure_Paediatric v0.55 NR1H4 Zornitza Stark Gene: nr1h4 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.54 NR1H4 Zornitza Stark gene: NR1H4 was added
gene: NR1H4 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: NR1H4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NR1H4 were set to 26888176; 32443034
Phenotypes for gene: NR1H4 were set to Cholestasis, progressive familial intrahepatic, 5, MIM# 617049
Review for gene: NR1H4 was set to GREEN
Added comment: Autosomal recessive severe liver disorder characterized by onset of intralobular cholestasis in the neonatal period. The disease is rapidly progressive, leading to liver failure and death if liver transplant is not performed. Other features include abnormal liver enzymes, low to normal gamma-glutamyl transferase (GGT) activity, increased alpha-fetoprotein, and a vitamin K-independent coagulopathy.

At least 5 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.53 JAG1 Zornitza Stark Marked gene: JAG1 as ready
Liver Failure_Paediatric v0.53 JAG1 Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.53 JAG1 Zornitza Stark Classified gene: JAG1 as Green List (high evidence)
Liver Failure_Paediatric v0.53 JAG1 Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.52 JAG1 Zornitza Stark gene: JAG1 was added
gene: JAG1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: JAG1 were set to Alagille syndrome, MIM# 118450
Review for gene: JAG1 was set to GREEN
Added comment: Well established gene disease association. Severity of liver disease is variable but includes progressive liver failure.
Sources: Expert list
Liver Failure_Paediatric v0.51 PTF1A Zornitza Stark Marked gene: PTF1A as ready
Liver Failure_Paediatric v0.51 PTF1A Zornitza Stark Gene: ptf1a has been classified as Red List (Low Evidence).
Liver Failure_Paediatric v0.51 PTF1A Zornitza Stark gene: PTF1A was added
gene: PTF1A was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: PTF1A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTF1A were set to 24212882
Phenotypes for gene: PTF1A were set to Pancreatic agenesis 2, MIM# 615935
Review for gene: PTF1A was set to RED
Added comment: 14 affected individuals from 10 families with isolated pancreatic hypoplasia or agenesis reported. Patients were typically diagnosed with insulin-dependent diabetes mellitus at birth or in infancy, although 2 individuals were diagnosed at ages 8 and 10 years, respectively, and 1 at 22 years of age. All patients also had pancreatic exocrine insufficiency, with low or undetectable stool elastase in all who were tested. Pancreatic hypoplasia or agenesis was documented by ultrasound, CT, or MRI in the 9 patients studied. No neurologic features were reported, except for 1 patient who exhibited mild developmental delay, and no other abnormalities were reported, except for 1 patient who had fatal cholestatic liver failure
Sources: Expert list
Liver Failure_Paediatric v0.50 FH Zornitza Stark Marked gene: FH as ready
Liver Failure_Paediatric v0.50 FH Zornitza Stark Gene: fh has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.50 FH Zornitza Stark Phenotypes for gene: FH were changed from to Fumarase deficiency, MIM#606812
Liver Failure_Paediatric v0.49 FH Zornitza Stark Classified gene: FH as Green List (high evidence)
Liver Failure_Paediatric v0.49 FH Zornitza Stark Gene: fh has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.48 FH Zornitza Stark edited their review of gene: FH: Changed phenotypes: Fumarase deficiency, MIM#606812
Liver Failure_Paediatric v0.48 FH Zornitza Stark gene: FH was added
gene: FH was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: FH was set to BIALLELIC, autosomal or pseudoautosomal
Review for gene: FH was set to GREEN
Added comment: Autosomal recessive metabolic disorder characterized by early-onset hypotonia, profound psychomotor retardation, and brain abnormalities, such as agenesis of the corpus callosum, gyral defects, and ventriculomegaly. Many patients show neonatal distress, metabolic acidosis, and/or encephalopathy. Cholestasis, liver fibrosis and failure reported.
Sources: Expert list
Liver Failure_Paediatric v0.47 TALDO1 Zornitza Stark Marked gene: TALDO1 as ready
Liver Failure_Paediatric v0.47 TALDO1 Zornitza Stark Gene: taldo1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.47 TALDO1 Zornitza Stark Classified gene: TALDO1 as Green List (high evidence)
Liver Failure_Paediatric v0.47 TALDO1 Zornitza Stark Gene: taldo1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.46 TALDO1 Zornitza Stark gene: TALDO1 was added
gene: TALDO1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: TALDO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TALDO1 were set to 29923087; 23315216; 26238251; 18331807
Phenotypes for gene: TALDO1 were set to Transaldolase deficiency, MIM#606003
Review for gene: TALDO1 was set to GREEN
Added comment: Typical features include intrauterine growth restriction, triangular face, loose wrinkly skin at birth, and development of progressive liver failure. More than 5 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.45 AKR1D1 Zornitza Stark Publications for gene: AKR1D1 were set to 12970144
Liver Failure_Paediatric v0.44 AKR1D1 Zornitza Stark edited their review of gene: AKR1D1: Changed publications: 12970144, 20522910; Changed phenotypes: Bile acid synthesis defect, congenital, 2, MIM# 235555
Liver Failure_Paediatric v0.44 AKR1D1 Zornitza Stark Marked gene: AKR1D1 as ready
Liver Failure_Paediatric v0.44 AKR1D1 Zornitza Stark Gene: akr1d1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.44 AKR1D1 Zornitza Stark Classified gene: AKR1D1 as Green List (high evidence)
Liver Failure_Paediatric v0.44 AKR1D1 Zornitza Stark Gene: akr1d1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.43 AKR1D1 Zornitza Stark gene: AKR1D1 was added
gene: AKR1D1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: AKR1D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AKR1D1 were set to 12970144
Phenotypes for gene: AKR1D1 were set to Bile acid synthesis defect, congenital, 2, MIM# 235555
Review for gene: AKR1D1 was set to GREEN
Added comment: Severe intrahepatic cholestasis progressing to liver failure. More than 3 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.42 SLC25A13 Zornitza Stark Marked gene: SLC25A13 as ready
Liver Failure_Paediatric v0.42 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.42 SLC25A13 Zornitza Stark Classified gene: SLC25A13 as Green List (high evidence)
Liver Failure_Paediatric v0.42 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.41 SLC25A13 Zornitza Stark gene: SLC25A13 was added
gene: SLC25A13 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: SLC25A13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A13 were set to 21424115; 11343052
Phenotypes for gene: SLC25A13 were set to Citrullinemia, type II, neonatal-onset, MIM# 605814
Review for gene: SLC25A13 was set to GREEN
Added comment: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive metabolic disorder characterized by poor growth, intrahepatic cholestasis, and increased serum citrulline. Most individuals show spontaneous improvement by 1 year of age. However, some individuals may have a progressive course with continued failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and some may develop chronic or fatal liver disease.

Well established gene-disease association.
Sources: Expert list
Liver Failure_Paediatric v0.40 SCYL1 Zornitza Stark Marked gene: SCYL1 as ready
Liver Failure_Paediatric v0.40 SCYL1 Zornitza Stark Gene: scyl1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.40 SCYL1 Zornitza Stark Classified gene: SCYL1 as Green List (high evidence)
Liver Failure_Paediatric v0.40 SCYL1 Zornitza Stark Gene: scyl1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.39 SCYL1 Zornitza Stark gene: SCYL1 was added
gene: SCYL1 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: SCYL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCYL1 were set to 26581903; 29419818; 30531813
Phenotypes for gene: SCYL1 were set to Spinocerebellar ataxia, autosomal recessive 21, MIM#616719
Review for gene: SCYL1 was set to GREEN
Added comment: Autosomal recessive spinocerebellar ataxia-21 is a neurologic disorder characterized by onset of cerebellar ataxia associated with cerebellar atrophy in early childhood. Affected individuals also have recurrent episodes of liver failure in the first decade, resulting in chronic liver fibrosis, as well as later onset of a peripheral neuropathy. Mild learning disabilities may also occur.

More than 5 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.38 MARS Zornitza Stark Marked gene: MARS as ready
Liver Failure_Paediatric v0.38 MARS Zornitza Stark Gene: mars has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.38 MARS Zornitza Stark Classified gene: MARS as Green List (high evidence)
Liver Failure_Paediatric v0.38 MARS Zornitza Stark Gene: mars has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.37 MARS Zornitza Stark gene: MARS was added
gene: MARS was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: MARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MARS were set to 24103465; 25913036
Phenotypes for gene: MARS were set to Interstitial lung and liver disease, MIM#615486
Review for gene: MARS was set to GREEN
Added comment: Autosomal recessive disorder characterized by onset of respiratory insufficiency and progressive liver disease in infancy or early childhood.

More than 5 unrelated families reported. Founder variants in Reunion Island, p.Ser567Leu and p.Ala393Thr, in cis.
Sources: Expert list
Liver Failure_Paediatric v0.36 ATP7B Zornitza Stark Marked gene: ATP7B as ready
Liver Failure_Paediatric v0.36 ATP7B Zornitza Stark Gene: atp7b has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.36 ATP7B Zornitza Stark Classified gene: ATP7B as Green List (high evidence)
Liver Failure_Paediatric v0.36 ATP7B Zornitza Stark Gene: atp7b has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.35 ATP7B Zornitza Stark gene: ATP7B was added
gene: ATP7B was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ATP7B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATP7B were set to Wilson disease, MIM#277900
Review for gene: ATP7B was set to GREEN
Added comment: Well established gene-disease association. Can present with liver failure in childhood.
Sources: Expert list
Liver Failure_Paediatric v0.34 SLC30A10 Zornitza Stark Marked gene: SLC30A10 as ready
Liver Failure_Paediatric v0.34 SLC30A10 Zornitza Stark Gene: slc30a10 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.34 SLC30A10 Zornitza Stark Classified gene: SLC30A10 as Green List (high evidence)
Liver Failure_Paediatric v0.34 SLC30A10 Zornitza Stark Gene: slc30a10 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.33 SLC30A10 Zornitza Stark changed review comment from: autosomal recessive metabolic disorder characterized by increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, which leads to cirrhosis in some cases. Intellectual function is preserved.

More than 10 unrelated families reported.
Sources: Expert list; to: Autosomal recessive metabolic disorder characterized by increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, which leads to cirrhosis in some cases. Intellectual function is preserved.

More than 10 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.33 SLC30A10 Zornitza Stark gene: SLC30A10 was added
gene: SLC30A10 was added to Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: SLC30A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A10 were set to 22341972; 22341971; 29193034
Phenotypes for gene: SLC30A10 were set to Hypermanganesemia with dystonia 1, MIM# 613280
Review for gene: SLC30A10 was set to GREEN
Added comment: autosomal recessive metabolic disorder characterized by increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, which leads to cirrhosis in some cases. Intellectual function is preserved.

More than 10 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.32 Zornitza Stark Panel name changed from Acute Liver Failure_Paediatric to Liver Failure_Paediatric
Liver Failure_Paediatric v0.31 MPI Zornitza Stark Marked gene: MPI as ready
Liver Failure_Paediatric v0.31 MPI Zornitza Stark Gene: mpi has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.31 MPI Zornitza Stark Classified gene: MPI as Green List (high evidence)
Liver Failure_Paediatric v0.31 MPI Zornitza Stark Gene: mpi has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.30 MPI Zornitza Stark gene: MPI was added
gene: MPI was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: MPI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPI were set to 25902754
Phenotypes for gene: MPI were set to Congenital disorder of glycosylation, type Ib, MIM# 602579
Review for gene: MPI was set to GREEN
Added comment: Hepatic involvement is prominent and liver failure reported.
Sources: Expert list
Liver Failure_Paediatric v0.29 LIPA Zornitza Stark Marked gene: LIPA as ready
Liver Failure_Paediatric v0.29 LIPA Zornitza Stark Gene: lipa has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.29 LIPA Zornitza Stark Classified gene: LIPA as Green List (high evidence)
Liver Failure_Paediatric v0.29 LIPA Zornitza Stark Gene: lipa has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.28 LIPA Zornitza Stark gene: LIPA was added
gene: LIPA was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: LIPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIPA were set to 8617513; 21963785
Phenotypes for gene: LIPA were set to Cholesteryl ester storage disease, MIM# 278000; Wolman disease, MIM# 278000
Review for gene: LIPA was set to GREEN
Added comment: Liver failure can be of early onset and rapidly progressive or more chronic.
Sources: Expert list
Liver Failure_Paediatric v0.27 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Liver Failure_Paediatric v0.27 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.27 NPC1 Zornitza Stark Classified gene: NPC1 as Green List (high evidence)
Liver Failure_Paediatric v0.27 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.26 NPC1 Zornitza Stark gene: NPC1 was added
gene: NPC1 was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPC1 were set to 25902754
Phenotypes for gene: NPC1 were set to Niemann-Pick disease, MIM# 257220
Review for gene: NPC1 was set to GREEN
Added comment: Rare presentations with liver failure reported.
Sources: Expert list
Liver Failure_Paediatric v0.25 TRMU Zornitza Stark Marked gene: TRMU as ready
Liver Failure_Paediatric v0.25 TRMU Zornitza Stark Gene: trmu has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.25 TRMU Zornitza Stark Classified gene: TRMU as Green List (high evidence)
Liver Failure_Paediatric v0.25 TRMU Zornitza Stark Gene: trmu has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.24 TRMU Zornitza Stark gene: TRMU was added
gene: TRMU was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: TRMU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRMU were set to 19732863
Phenotypes for gene: TRMU were set to Liver failure, transient infantile, MIM# 613070
Review for gene: TRMU was set to GREEN
Added comment: Acute infantile liver failure resulting from variants in TRMU is a transient disorder of hepatic function. In addition to elevated liver enzymes, jaundice, vomiting, coagulopathy, and hyperbilirubinemia, the presence of increased serum lactate is consistent with a defect in mitochondrial respiratory function. With supportive care, patients who survive the initial acute episode can recover and show normal development.

Thirteen individuals reported, including 7 of Yemenite Jewish origin with same recurrent founder variant, p.Tyr77His.
Sources: Expert list
Liver Failure_Paediatric v0.23 RINT1 Zornitza Stark Marked gene: RINT1 as ready
Liver Failure_Paediatric v0.23 RINT1 Zornitza Stark Gene: rint1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.23 RINT1 Zornitza Stark Classified gene: RINT1 as Green List (high evidence)
Liver Failure_Paediatric v0.23 RINT1 Zornitza Stark Gene: rint1 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.22 RINT1 Zornitza Stark gene: RINT1 was added
gene: RINT1 was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: RINT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RINT1 were set to 31204009
Phenotypes for gene: RINT1 were set to Infantile liver failure syndrome 3, MIM# 618641
Review for gene: RINT1 was set to GREEN
Added comment: Recurrent episodes of acute liver failure during intercurrent febrile illness. Patients first present in infancy or early childhood, and there usually is complete recovery between episodes with conservative treatment. Affected individuals also have skeletal anomalies of the vertebral bodies and femoral heads.

Three unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.21 LARS Zornitza Stark Marked gene: LARS as ready
Liver Failure_Paediatric v0.21 LARS Zornitza Stark Gene: lars has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.21 LARS Zornitza Stark Classified gene: LARS as Green List (high evidence)
Liver Failure_Paediatric v0.21 LARS Zornitza Stark Gene: lars has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.20 LARS Zornitza Stark gene: LARS was added
gene: LARS was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: LARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LARS were set to 30349989
Phenotypes for gene: LARS were set to Infantile liver failure syndrome 1, MIM# 615438
Review for gene: LARS was set to GREEN
Added comment: Six unrelated families reported in the literature, reviewed in PMID: 30349989.
Sources: Expert list
Liver Failure_Paediatric v0.19 NBAS Zornitza Stark Marked gene: NBAS as ready
Liver Failure_Paediatric v0.19 NBAS Zornitza Stark Gene: nbas has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.19 NBAS Zornitza Stark Classified gene: NBAS as Green List (high evidence)
Liver Failure_Paediatric v0.19 NBAS Zornitza Stark Gene: nbas has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.18 NBAS Zornitza Stark gene: NBAS was added
gene: NBAS was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: NBAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NBAS were set to 26073778
Phenotypes for gene: NBAS were set to Infantile liver failure syndrome 2, MIM# 616483
Review for gene: NBAS was set to GREEN
Added comment: Recurrent episodes of acute liver failure during intercurrent febrile illness. More than 10 unrelated families reported.
Sources: Expert list
Liver Failure_Paediatric v0.17 OTC Zornitza Stark Marked gene: OTC as ready
Liver Failure_Paediatric v0.17 OTC Zornitza Stark Gene: otc has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.17 OTC Zornitza Stark Classified gene: OTC as Green List (high evidence)
Liver Failure_Paediatric v0.17 OTC Zornitza Stark Gene: otc has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.16 OTC Zornitza Stark gene: OTC was added
gene: OTC was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: OTC was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: OTC were set to 28887792; 25902754
Phenotypes for gene: OTC were set to Ornithine transcarbamylase deficiency, MIM# 311250
Review for gene: OTC was set to GREEN
Added comment: Well established gene disease association.

Reports of presentations with liver failure.
Sources: Expert list
Liver Failure_Paediatric v0.15 MPV17 Zornitza Stark Marked gene: MPV17 as ready
Liver Failure_Paediatric v0.15 MPV17 Zornitza Stark Gene: mpv17 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.15 MPV17 Zornitza Stark Classified gene: MPV17 as Green List (high evidence)
Liver Failure_Paediatric v0.15 MPV17 Zornitza Stark Gene: mpv17 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.14 MPV17 Zornitza Stark gene: MPV17 was added
gene: MPV17 was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: MPV17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPV17 were set to 18695062
Phenotypes for gene: MPV17 were set to Mitochondrial DNA depletion syndrome 6 (hepatocerebral type), MIM# 256810
Review for gene: MPV17 was set to GREEN
Added comment: Well established gene-disease association.

Mitochondrial DNA depletion syndrome-6 is an autosomal recessive disorder characterized by infantile onset of progressive liver failure, often leading to death in the first year of life. Those that survive develop progressive neurologic involvement, including ataxia, hypotonia, dystonia, and psychomotor regression.
Sources: Expert list
Liver Failure_Paediatric v0.13 DGUOK Zornitza Stark Marked gene: DGUOK as ready
Liver Failure_Paediatric v0.13 DGUOK Zornitza Stark Gene: dguok has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.13 DGUOK Zornitza Stark Classified gene: DGUOK as Green List (high evidence)
Liver Failure_Paediatric v0.13 DGUOK Zornitza Stark Gene: dguok has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.12 DGUOK Zornitza Stark Classified gene: DGUOK as Green List (high evidence)
Liver Failure_Paediatric v0.12 DGUOK Zornitza Stark Gene: dguok has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.11 DGUOK Zornitza Stark gene: DGUOK was added
gene: DGUOK was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: DGUOK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DGUOK were set to Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), MIM#251880
Review for gene: DGUOK was set to GREEN
Added comment: Well established gene-disease association.

Mitochondrial DNA depletion syndrome-3 is a severe autosomal recessive disorder characterized by onset in infancy of progressive liver failure and neurologic abnormalities, hypoglycemia, and increased lactate in body fluids. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes (I, III, IV, and V) and mtDNA depletion.
Sources: Expert list
Liver Failure_Paediatric v0.10 POLG Zornitza Stark Marked gene: POLG as ready
Liver Failure_Paediatric v0.10 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.10 POLG Zornitza Stark Classified gene: POLG as Green List (high evidence)
Liver Failure_Paediatric v0.10 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.9 POLG Zornitza Stark gene: POLG was added
gene: POLG was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: POLG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLG were set to 20220442
Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4A (Alpers type), MIM# 203700
Review for gene: POLG was set to GREEN
Added comment: Well established gene-disease association.

Alpers syndrome is an autosomal recessive disorder characterized by a clinical triad of psychomotor retardation, intractable epilepsy, and liver failure in infants and young children. Pathologic findings include neuronal loss in the cerebral gray matter with reactive astrocytosis and liver cirrhosis. The disorder is progressive and often leads to death from hepatic failure or status epilepticus before age 3 years.
Sources: Expert list
Liver Failure_Paediatric v0.8 ACADM Zornitza Stark Marked gene: ACADM as ready
Liver Failure_Paediatric v0.8 ACADM Zornitza Stark Gene: acadm has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.8 ACADM Zornitza Stark Classified gene: ACADM as Green List (high evidence)
Liver Failure_Paediatric v0.8 ACADM Zornitza Stark Gene: acadm has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.7 ACADM Zornitza Stark gene: ACADM was added
gene: ACADM was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ACADM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ACADM were set to Acyl-CoA dehydrogenase, medium chain, deficiency of, MIM# 201450
Review for gene: ACADM was set to GREEN
Added comment: Inherited deficiency of medium-chain acyl-CoA dehydrogenase is characterized by intolerance to prolonged fasting, recurrent episodes of hypoglycemic coma with medium-chain dicarboxylic aciduria, impaired ketogenesis, and low plasma and tissue carnitine levels. Can progress to liver failure.
Sources: Expert list
Liver Failure_Paediatric v0.6 ALDOB Zornitza Stark Marked gene: ALDOB as ready
Liver Failure_Paediatric v0.6 ALDOB Zornitza Stark Gene: aldob has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.6 ALDOB Zornitza Stark Classified gene: ALDOB as Green List (high evidence)
Liver Failure_Paediatric v0.6 ALDOB Zornitza Stark Gene: aldob has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.5 ALDOB Zornitza Stark gene: ALDOB was added
gene: ALDOB was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: ALDOB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ALDOB were set to Fructose intolerance, hereditary, MIM# 229600
Review for gene: ALDOB was set to GREEN
Added comment: Well established gene-disease association.

Hereditary fructose intolerance (HFI) becomes apparent in infancy at the time of weaning, when fructose or sucrose is added to the diet. Clinical features include recurrent vomiting, abdominal pain, and hypoglycemia that may be fatal. Long-term exposure to fructose can result in liver failure, renal tubulopathy, and growth retardation.
Sources: Expert list
Liver Failure_Paediatric v0.4 FAH Zornitza Stark Marked gene: FAH as ready
Liver Failure_Paediatric v0.4 FAH Zornitza Stark Gene: fah has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.4 FAH Zornitza Stark Classified gene: FAH as Green List (high evidence)
Liver Failure_Paediatric v0.4 FAH Zornitza Stark Gene: fah has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.3 FAH Zornitza Stark gene: FAH was added
gene: FAH was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: FAH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAH were set to 15759101
Phenotypes for gene: FAH were set to Tyrosinemia, type I, MIM#276700
Review for gene: FAH was set to GREEN
Added comment: Well established gene-disease association.

The disorder is characterized by progressive liver disease and a secondary renal tubular dysfunction leading to hypophosphatemic rickets. Onset varies from infancy to adolescence. In the most acute form patients present with severe liver failure within weeks after birth, whereas rickets may be the major symptom in chronic tyrosinemia. Untreated, death ensues from cirrhosis or hepatocellular carcinoma at a young age.
Sources: Expert list
Liver Failure_Paediatric v0.2 GALT Zornitza Stark Marked gene: GALT as ready
Liver Failure_Paediatric v0.2 GALT Zornitza Stark Gene: galt has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.2 GALT Zornitza Stark Classified gene: GALT as Green List (high evidence)
Liver Failure_Paediatric v0.2 GALT Zornitza Stark Gene: galt has been classified as Green List (High Evidence).
Liver Failure_Paediatric v0.1 GALT Zornitza Stark gene: GALT was added
gene: GALT was added to Acute Liver Failure_Paediatric. Sources: Expert list
Mode of inheritance for gene: GALT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GALT were set to Galactosaemia, MIM#230400
Review for gene: GALT was set to GREEN
Added comment: Well established gene-disease association. Most individuals present in the neonatal period, after ingestion of galactose, with jaundice, hepatosplenomegaly, hepatocellular insufficiency, food intolerance, hypoglycemia, renal tubular dysfunction, muscle hypotonia, sepsis, and cataract. Long-term complications include intellectual disability, verbal dyspraxia, motor abnormalities, and hypergonadotropic hypogonadism.

Commonly part of newborn screening program but currently not in Victoria.
Sources: Expert list
Liver Failure_Paediatric v0.0 Zornitza Stark Added Panel Acute Liver Failure_Paediatric
Set panel types to: Victorian Clinical Genetics Services; Rare Disease