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Congenital ophthalmoplegia v1.8 HNRNPA2B1 Zornitza Stark Phenotypes for gene: HNRNPA2B1 were changed from oculopharyngeal muscular dystrophy, MONDO:0008116 to oculopharyngeal muscular dystrophy, MONDO:0008116, OMIM#620460
Congenital ophthalmoplegia v1.7 Zornitza Stark List of related panels changed from to Abnormality of eye movement; HP:0000496
Congenital ophthalmoplegia v1.6 COLQ Zornitza Stark Tag treatable tag was added to gene: COLQ.
Tag clinical trial tag was added to gene: COLQ.
Congenital ophthalmoplegia v1.6 CHRNE Zornitza Stark Tag treatable tag was added to gene: CHRNE.
Congenital ophthalmoplegia v1.6 CHRND Zornitza Stark Tag treatable tag was added to gene: CHRND.
Congenital ophthalmoplegia v1.6 CHRNA1 Zornitza Stark Tag treatable tag was added to gene: CHRNA1.
Congenital ophthalmoplegia v1.6 CHAT Zornitza Stark Tag treatable tag was added to gene: CHAT.
Congenital ophthalmoplegia v1.6 MYO9A Zornitza Stark Classified gene: MYO9A as Amber List (moderate evidence)
Congenital ophthalmoplegia v1.6 MYO9A Zornitza Stark Gene: myo9a has been classified as Amber List (Moderate Evidence).
Congenital ophthalmoplegia v1.5 MYO9A Zornitza Stark edited their review of gene: MYO9A: Added comment: This gene-disease association has been reviewed as part of GenCC discordance resolution: note at least two of the variants reported have homozygotes with gnomad, which would be out of keeping for a severe paediatric disorder.; Changed rating: AMBER; Changed phenotypes: Myasthenic syndrome, congenital, 24, presynaptic, MIM# 618198
Congenital ophthalmoplegia v1.5 HNRNPA2B1 Zornitza Stark Marked gene: HNRNPA2B1 as ready
Congenital ophthalmoplegia v1.5 HNRNPA2B1 Zornitza Stark Gene: hnrnpa2b1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v1.5 HNRNPA2B1 Zornitza Stark Classified gene: HNRNPA2B1 as Green List (high evidence)
Congenital ophthalmoplegia v1.5 HNRNPA2B1 Zornitza Stark Gene: hnrnpa2b1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v1.4 HNRNPA2B1 Naomi Baker gene: HNRNPA2B1 was added
gene: HNRNPA2B1 was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: HNRNPA2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPA2B1 were set to PMID:35484142
Phenotypes for gene: HNRNPA2B1 were set to oculopharyngeal muscular dystrophy, MONDO:0008116
Review for gene: HNRNPA2B1 was set to GREEN
Added comment: PMID:35484142 reports 11 individuals from 10 families with heterozygous frameshift variants that result in the identical protein extension. Phenotype presents as an early-onset oculopharyngeal muscular dystrophy-like phenotype, and includes ptosis, ophthalmoplegia, symmetric proximal and distal weakness, moderate progression, dysphagia, respiratory insufficiency.
Sources: Literature
Congenital ophthalmoplegia v1.4 COL25A1 Zornitza Stark Publications for gene: COL25A1 were set to 25500261; 26486031
Congenital ophthalmoplegia v1.3 COL25A1 Zornitza Stark Classified gene: COL25A1 as Green List (high evidence)
Congenital ophthalmoplegia v1.3 COL25A1 Zornitza Stark Gene: col25a1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v1.2 COL25A1 Melanie Marty reviewed gene: COL25A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25500261, 26486031, 31875546, 26437029; Phenotypes: Fibrosis of extraocular muscles, congenital, 5, 610004; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v1.2 TUBA1A Sue White Marked gene: TUBA1A as ready
Congenital ophthalmoplegia v1.2 TUBA1A Sue White Gene: tuba1a has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v1.2 TUBA1A Sue White Classified gene: TUBA1A as Green List (high evidence)
Congenital ophthalmoplegia v1.2 TUBA1A Sue White Gene: tuba1a has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v1.1 TUBA1A Kristin Rigbye gene: TUBA1A was added
gene: TUBA1A was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: TUBA1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA1A were set to 30677308
Phenotypes for gene: TUBA1A were set to Congenital fibrosis of the extraocular muscles, AD
Review for gene: TUBA1A was set to GREEN
Added comment: PMID: 30677308 New genotype-phenotype correlation - congenital fibrosis of the extraocular muscles (CFEOM), with or without malformations of cortical brain development.

3 unrelated probands with CFEOM who harbored novel heterozygous TUBA1A missense variants c.1216C>G, p.(His406Asp); c.467G>A, p.(Arg156His); and c.1193T>G, p.(Met398Arg). MRI revealed small oculomotor-innervated muscles and asymmetrical caudate heads and lateral ventricles with or without corpus callosal thinning. Two of the three probands had MCD. Infantile onset.

Distinct missense variants in the beta-tubulin encoding genes TUBB3 and TUBB2B cause MCD, CFEOM, or both, suggesting substitution-specific mechanisms.
Sources: Literature
Congenital ophthalmoplegia v1.0 Zornitza Stark promoted panel to version 1.0
Congenital ophthalmoplegia v0.93 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Congenital ophthalmoplegia v0.92 MYO9A Zornitza Stark Marked gene: MYO9A as ready
Congenital ophthalmoplegia v0.92 MYO9A Zornitza Stark Gene: myo9a has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.92 MYO9A Zornitza Stark Classified gene: MYO9A as Green List (high evidence)
Congenital ophthalmoplegia v0.92 MYO9A Zornitza Stark Gene: myo9a has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.91 MYO9A Zornitza Stark gene: MYO9A was added
gene: MYO9A was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: MYO9A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MYO9A were set to Myasthenic syndrome, congenital, 24, presynaptic, MIM# 618198
Review for gene: MYO9A was set to GREEN
Added comment: Ptosis and ophthalmoplegia are common features of CMS.
Sources: Expert list
Congenital ophthalmoplegia v0.90 CHRND Zornitza Stark Marked gene: CHRND as ready
Congenital ophthalmoplegia v0.90 CHRND Zornitza Stark Gene: chrnd has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.90 CHRND Zornitza Stark Classified gene: CHRND as Green List (high evidence)
Congenital ophthalmoplegia v0.90 CHRND Zornitza Stark Gene: chrnd has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.89 CHRND Zornitza Stark gene: CHRND was added
gene: CHRND was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: CHRND was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CHRND were set to Myasthenic syndrome, congenital, 3B, fast-channel, MIM# 616322
Review for gene: CHRND was set to GREEN
Added comment: Ptosis and ophthalmoplegia are features of congenital myasthenic syndromes.
Sources: Expert list
Congenital ophthalmoplegia v0.87 LMOD3 Zornitza Stark Marked gene: LMOD3 as ready
Congenital ophthalmoplegia v0.87 LMOD3 Zornitza Stark Gene: lmod3 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.87 LMOD3 Zornitza Stark Classified gene: LMOD3 as Green List (high evidence)
Congenital ophthalmoplegia v0.87 LMOD3 Zornitza Stark Gene: lmod3 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.86 LMOD3 Zornitza Stark gene: LMOD3 was added
gene: LMOD3 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: LMOD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMOD3 were set to 25250574
Phenotypes for gene: LMOD3 were set to Nemaline myopathy 10, MIM# 616165
Review for gene: LMOD3 was set to GREEN
Added comment: In a series of 21 affected individuals, ophthalmoplegia was present in a third.
Sources: Expert list
Congenital ophthalmoplegia v0.83 HPDL Zornitza Stark changed review comment from: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA) is an autosomal recessive disorder characterized by impaired psychomotor development apparent in infancy. Affected individuals show poor overall growth, progressive microcephaly, and axial hypotonia, with later onset of spasticity. The disorder is progressive. Some patients show normal early development, but later have regression of motor, cognitive, and language skills. More variable features include seizures, joint contractures, ocular disturbances including ophthalmoplegia, episodic respiratory failure, and nonspecific dysmorphic facial features.
Sources: Expert list; to: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA) is an autosomal recessive disorder characterized by impaired psychomotor development apparent in infancy. Affected individuals show poor overall growth, progressive microcephaly, and axial hypotonia, with later onset of spasticity. The disorder is progressive. Some patients show normal early development, but later have regression of motor, cognitive, and language skills. More variable features include seizures, joint contractures, ocular disturbances including ophthalmoplegia, episodic respiratory failure, and nonspecific dysmorphic facial features. Nine unrelated families.
Sources: Expert list
Congenital ophthalmoplegia v0.83 HPDL Zornitza Stark Marked gene: HPDL as ready
Congenital ophthalmoplegia v0.83 HPDL Zornitza Stark Gene: hpdl has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.83 HPDL Zornitza Stark Classified gene: HPDL as Green List (high evidence)
Congenital ophthalmoplegia v0.83 HPDL Zornitza Stark Gene: hpdl has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.82 HPDL Zornitza Stark gene: HPDL was added
gene: HPDL was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPDL were set to 32707086
Phenotypes for gene: HPDL were set to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MIM# 619026
Review for gene: HPDL was set to GREEN
Added comment: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA) is an autosomal recessive disorder characterized by impaired psychomotor development apparent in infancy. Affected individuals show poor overall growth, progressive microcephaly, and axial hypotonia, with later onset of spasticity. The disorder is progressive. Some patients show normal early development, but later have regression of motor, cognitive, and language skills. More variable features include seizures, joint contractures, ocular disturbances including ophthalmoplegia, episodic respiratory failure, and nonspecific dysmorphic facial features.
Sources: Expert list
Congenital ophthalmoplegia v0.79 SURF1 Zornitza Stark Marked gene: SURF1 as ready
Congenital ophthalmoplegia v0.79 SURF1 Zornitza Stark Gene: surf1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.79 SURF1 Zornitza Stark Classified gene: SURF1 as Green List (high evidence)
Congenital ophthalmoplegia v0.79 SURF1 Zornitza Stark Gene: surf1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.78 SLC18A3 Zornitza Stark Marked gene: SLC18A3 as ready
Congenital ophthalmoplegia v0.78 SLC18A3 Zornitza Stark Gene: slc18a3 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.78 SLC18A3 Zornitza Stark Classified gene: SLC18A3 as Green List (high evidence)
Congenital ophthalmoplegia v0.78 SLC18A3 Zornitza Stark Gene: slc18a3 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.77 C1QBP Zornitza Stark Marked gene: C1QBP as ready
Congenital ophthalmoplegia v0.77 C1QBP Zornitza Stark Gene: c1qbp has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.77 C1QBP Zornitza Stark Classified gene: C1QBP as Green List (high evidence)
Congenital ophthalmoplegia v0.77 C1QBP Zornitza Stark Gene: c1qbp has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.76 BIN1 Zornitza Stark Marked gene: BIN1 as ready
Congenital ophthalmoplegia v0.76 BIN1 Zornitza Stark Gene: bin1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.76 BIN1 Zornitza Stark Classified gene: BIN1 as Green List (high evidence)
Congenital ophthalmoplegia v0.76 BIN1 Zornitza Stark Gene: bin1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.75 C1QBP Shannon LeBlanc gene: C1QBP was added
gene: C1QBP was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: C1QBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C1QBP were set to PMID: 28942965
Phenotypes for gene: C1QBP were set to Combined oxidative phosphorylation deficiency 33, MIM# 617713
Review for gene: C1QBP was set to GREEN
Added comment: Highly variable, ranging from death in infancy to adult-onset progressive external ophthalmoplegia (PEO) and myopathy. PEO onset has been reported in childhood.
Sources: Literature
Congenital ophthalmoplegia v0.75 SLC18A3 Shannon LeBlanc gene: SLC18A3 was added
gene: SLC18A3 was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: SLC18A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC18A3 were set to PMID: 27590285; 20123977; 28188302; 31059209
Phenotypes for gene: SLC18A3 were set to Myasthenic syndrome, congenital, 21, presynaptic OMIM 617239
Review for gene: SLC18A3 was set to GREEN
Added comment: congenital myasthenic syndrome - ptosis and ophthalmoplegia are common features.

Three families with bi-allelic variants and a mouse model support gene-disease association. Fetal akinesia reported in association with LOF variants.
Sources: Literature
Congenital ophthalmoplegia v0.75 SUCLA2 Zornitza Stark Marked gene: SUCLA2 as ready
Congenital ophthalmoplegia v0.75 SUCLA2 Zornitza Stark Gene: sucla2 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.75 SUCLA2 Zornitza Stark Phenotypes for gene: SUCLA2 were changed from to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) OMIM 612073
Congenital ophthalmoplegia v0.74 SUCLA2 Zornitza Stark Classified gene: SUCLA2 as Green List (high evidence)
Congenital ophthalmoplegia v0.74 SUCLA2 Zornitza Stark Gene: sucla2 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.73 BIN1 Shannon LeBlanc gene: BIN1 was added
gene: BIN1 was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: BIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BIN1 were set to PMID 29950440
Phenotypes for gene: BIN1 were set to Centronuclear myopathy 2, MIM 255200
Review for gene: BIN1 was set to GREEN
Added comment: Wide range at onset from neonatal to adulthood with usually mild, slowly progressive proximal limb weakness and ophthalmoparesis
Sources: Literature
Congenital ophthalmoplegia v0.73 SUCLA2 Shannon LeBlanc reviewed gene: SUCLA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301762; Phenotypes: Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) OMIM 612073; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.73 SUCLA2 Shannon LeBlanc Deleted their review
Congenital ophthalmoplegia v0.73 SUCLA2 Shannon LeBlanc gene: SUCLA2 was added
gene: SUCLA2 was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: SUCLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUCLA2 were set to PMID: 20301762
Review for gene: SUCLA2 was set to GREEN
Added comment: Infantile onset. External ophthalmoplegia is feature in up to 25% of patients.
Sources: Literature
Congenital ophthalmoplegia v0.73 SURF1 Shannon LeBlanc gene: SURF1 was added
gene: SURF1 was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: SURF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SURF1 were set to PMID: 10746561; 29933018; 33134083
Phenotypes for gene: SURF1 were set to Mitochondrial complex IV deficiency, nuclear type 1 OMIM 220110
Review for gene: SURF1 was set to GREEN
Added comment: Oculomotor abnormalities such as slow saccades, ophthalmoparesis or complex irregular eye movements are a feature.
Sources: Literature
Congenital ophthalmoplegia v0.73 Zornitza Stark Panel types changed to Rare Disease
Congenital ophthalmoplegia v0.72 MYF5 Zornitza Stark Publications for gene: MYF5 were set to PMID: 29887215
Congenital ophthalmoplegia v0.71 MYF5 Zornitza Stark Marked gene: MYF5 as ready
Congenital ophthalmoplegia v0.71 MYF5 Zornitza Stark Gene: myf5 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.71 MYF5 Zornitza Stark Classified gene: MYF5 as Green List (high evidence)
Congenital ophthalmoplegia v0.71 MYF5 Zornitza Stark Gene: myf5 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.70 DGUOK Zornitza Stark Marked gene: DGUOK as ready
Congenital ophthalmoplegia v0.70 DGUOK Zornitza Stark Gene: dguok has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.70 DGUOK Zornitza Stark Classified gene: DGUOK as Green List (high evidence)
Congenital ophthalmoplegia v0.70 DGUOK Zornitza Stark Gene: dguok has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.69 RRM2B Zornitza Stark Marked gene: RRM2B as ready
Congenital ophthalmoplegia v0.69 RRM2B Zornitza Stark Gene: rrm2b has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.69 RRM2B Zornitza Stark Classified gene: RRM2B as Green List (high evidence)
Congenital ophthalmoplegia v0.69 RRM2B Zornitza Stark Gene: rrm2b has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.68 POLG2 Zornitza Stark Marked gene: POLG2 as ready
Congenital ophthalmoplegia v0.68 POLG2 Zornitza Stark Gene: polg2 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.68 POLG2 Zornitza Stark Publications for gene: POLG2 were set to PMID: 21555342; 16685652
Congenital ophthalmoplegia v0.67 POLG2 Zornitza Stark Classified gene: POLG2 as Green List (high evidence)
Congenital ophthalmoplegia v0.67 POLG2 Zornitza Stark Gene: polg2 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.66 POLG2 Shannon LeBlanc gene: POLG2 was added
gene: POLG2 was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: POLG2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POLG2 were set to PMID: 21555342; 16685652
Phenotypes for gene: POLG2 were set to Mitochondrial DNA depletion syndrome 16 (hepatic type) - 618528; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 - 610131
Review for gene: POLG2 was set to GREEN
Added comment: PEOA4 - age of onset range from infancy to adulthood.
Sources: Literature
Congenital ophthalmoplegia v0.66 RRM2B Shannon LeBlanc gene: RRM2B was added
gene: RRM2B was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: RRM2B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RRM2B were set to PMID: 17486094; 19138848; 24741716; 31462754
Phenotypes for gene: RRM2B were set to Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) - 612075; Mitochondrial DNA depletion syndrome 8B (MNGIE type) - 612075; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5 - 613077
Review for gene: RRM2B was set to GREEN
Added comment: Neonatal onset. Ophthalmoplegia and ptosis are common features.
Sources: Literature
Congenital ophthalmoplegia v0.66 DGUOK Shannon LeBlanc gene: DGUOK was added
gene: DGUOK was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: DGUOK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DGUOK were set to PMID: 11687800; 12205643; 15887277
Phenotypes for gene: DGUOK were set to Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), OMIM 251880; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4, OMIM 617070; portal hypertension, non cirrhotic OMIM 617068
Review for gene: DGUOK was set to GREEN
Added comment: Mitochondrial DNA depletion syndrome-3: onset in infancy, progressive external ophthalmoplegia is a feature.
Sources: Literature
Congenital ophthalmoplegia v0.66 MYF5 Shannon LeBlanc gene: MYF5 was added
gene: MYF5 was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: MYF5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYF5 were set to PMID: 29887215
Phenotypes for gene: MYF5 were set to Ophthalmoplegia, external, with rib and vertebral anomalies, OMIM 61855
Review for gene: MYF5 was set to GREEN
Added comment: congenital non-progressive external ophthalmoplegia and ptosis. Other features include hypoplastic or missing ribs with fusion anomalies. Torticollis and scoliosis develops during childhood.

PMID 29887215: three unrelated consanguineous families with homozygous LOF mutations: Two Turkish families with a homozygous 10bp deletion (frameshift), predicted to undergo NMD. Two sisters from a Yemeni family with a homozygous missense variant in exon 1 - in vitro assays showed LOF for the missense variant.

The clinical phenotype overlaps strikingly with several MYF5 knockout mouse models. (PMID: 15386014, 1423602, 9268580, 8918877).
Sources: Literature
Congenital ophthalmoplegia v0.66 RYR1 Zornitza Stark Marked gene: RYR1 as ready
Congenital ophthalmoplegia v0.66 RYR1 Zornitza Stark Gene: ryr1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.66 RYR1 Zornitza Stark Classified gene: RYR1 as Green List (high evidence)
Congenital ophthalmoplegia v0.66 RYR1 Zornitza Stark Gene: ryr1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.65 POLG Zornitza Stark Marked gene: POLG as ready
Congenital ophthalmoplegia v0.65 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.65 POLG Zornitza Stark Classified gene: POLG as Green List (high evidence)
Congenital ophthalmoplegia v0.65 POLG Zornitza Stark Gene: polg has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.64 MYH2 Zornitza Stark Marked gene: MYH2 as ready
Congenital ophthalmoplegia v0.64 MYH2 Zornitza Stark Gene: myh2 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.64 MYH2 Zornitza Stark Phenotypes for gene: MYH2 were changed from to Proximal myopathy and ophthalmoplegia, MIM# 605637
Congenital ophthalmoplegia v0.63 MYH2 Zornitza Stark Classified gene: MYH2 as Green List (high evidence)
Congenital ophthalmoplegia v0.63 MYH2 Zornitza Stark Gene: myh2 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.62 MYH2 Zornitza Stark reviewed gene: MYH2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Proximal myopathy and ophthalmoplegia, MIM# 605637; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.62 TYMP Zornitza Stark reviewed gene: TYMP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 1 (MNGIE type) 603041; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.62 TYMP Zornitza Stark Marked gene: TYMP as ready
Congenital ophthalmoplegia v0.62 TYMP Zornitza Stark Gene: tymp has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.62 TYMP Zornitza Stark Classified gene: TYMP as Green List (high evidence)
Congenital ophthalmoplegia v0.62 TYMP Zornitza Stark Gene: tymp has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.61 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Congenital ophthalmoplegia v0.61 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.61 NPC1 Zornitza Stark Classified gene: NPC1 as Green List (high evidence)
Congenital ophthalmoplegia v0.61 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.60 TWNK Zornitza Stark Marked gene: TWNK as ready
Congenital ophthalmoplegia v0.60 TWNK Zornitza Stark Gene: twnk has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.60 TWNK Zornitza Stark Classified gene: TWNK as Green List (high evidence)
Congenital ophthalmoplegia v0.60 TWNK Zornitza Stark Gene: twnk has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.59 TWNK Shannon LeBlanc gene: TWNK was added
gene: TWNK was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: TWNK was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TWNK were set to PMID 17921179; 32234020
Phenotypes for gene: TWNK were set to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) 271245; Perrault syndrome 5 616138; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 609286
Review for gene: TWNK was set to GREEN
Added comment: Mitochondrial DNA depletion syndrome-7: biallelic, severe neurodegenerative disorder characterized primarily by hypotonia, ataxia, ophthalmoplegia, hearing loss, seizures, and sensory axonal neuropathy. Infantile onset

PMID: 32234020: Fig 1 shows the variant distribution for various phenotypes
Sources: Literature
Congenital ophthalmoplegia v0.59 NPC1 Shannon LeBlanc gene: NPC1 was added
gene: NPC1 was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NPC1 were set to Niemann-Pick disease, type C, 257220
Review for gene: NPC1 was set to GREEN
Added comment: Well established gene-disease association.

Vertical supranuclear gaze palsy is an early manifestation in childhood-onset type.
Sources: Literature
Congenital ophthalmoplegia v0.59 TYMP Shannon LeBlanc gene: TYMP was added
gene: TYMP was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: TYMP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TYMP were set to PMID: 21933806; 30775048
Phenotypes for gene: TYMP were set to Mitochondrial DNA depletion syndrome 1 (MNGIE type) 603041
Added comment: Ophthalmoplegia is a common feature.

age of onset range 5 months to 35 years); however, the majority of patients reported the first symptoms before the age of 12 years.

Garone 2011: 92 patients with biallelic variants
Sources: Literature
Congenital ophthalmoplegia v0.59 MYH2 Shannon LeBlanc gene: MYH2 was added
gene: MYH2 was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: MYH2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYH2 were set to PMID 24193343; 32578970; 11114175; 23489661
Added comment: childhood consent ophthalmoplegia and progressive proximal limb weakness. Either slowly progressive or non-progressive.

> 10 families reported with balletic variants
monoallelic variants: two missense variants reported
Sources: Literature
Congenital ophthalmoplegia v0.59 POLG Shannon LeBlanc gene: POLG was added
gene: POLG was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: POLG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4A (Alpers type) MIM#203700; Mitochondrial DNA depletion syndrome 4B (MNGIE type) MIM#613662; Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) MIM#607459; Progressive external ophthalmoplegia, autosomal recessive 1 MIM#258450
Review for gene: POLG was set to GREEN
Added comment: Well established gene-disease associaition. Variable age of onset of ophthalmoplegia, including infancy and early childhood.
Sources: Literature
Congenital ophthalmoplegia v0.59 RYR1 Shannon LeBlanc gene: RYR1 was added
gene: RYR1 was added to Congenital ophthalmoplegia. Sources: Literature
Mode of inheritance for gene: RYR1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RYR1 were set to Minicore myopathy with external ophthalmoplegia 255320
Review for gene: RYR1 was set to GREEN
Added comment: ophthalmoplegia is a common features. Also presents with congenital myopathy, including neonatal hypotonia, delayed motor development, and generalized muscle weakness and amyotrophy,
Sources: Literature
Congenital ophthalmoplegia v0.59 CHRNE Zornitza Stark Marked gene: CHRNE as ready
Congenital ophthalmoplegia v0.59 CHRNE Zornitza Stark Gene: chrne has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.59 CHRNE Zornitza Stark Classified gene: CHRNE as Green List (high evidence)
Congenital ophthalmoplegia v0.59 CHRNE Zornitza Stark Gene: chrne has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.58 CHRNE Zornitza Stark gene: CHRNE was added
gene: CHRNE was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: CHRNE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CHRNE were set to Myasthenic syndrome, congenital, 4B, fast-channel, MIM# 616324
Review for gene: CHRNE was set to GREEN
Added comment: Ophthalmoplegia is a feature.
Sources: Expert list
Congenital ophthalmoplegia v0.57 CHRNB1 Zornitza Stark Marked gene: CHRNB1 as ready
Congenital ophthalmoplegia v0.57 CHRNB1 Zornitza Stark Gene: chrnb1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.57 CHRNB1 Zornitza Stark Classified gene: CHRNB1 as Green List (high evidence)
Congenital ophthalmoplegia v0.57 CHRNB1 Zornitza Stark Gene: chrnb1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.56 CHRNB1 Zornitza Stark gene: CHRNB1 was added
gene: CHRNB1 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: CHRNB1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CHRNB1 were set to Myasthenic syndrome, congenital, 2A, slow-channel, MIM# 616313
Review for gene: CHRNB1 was set to GREEN
Added comment: Ophthalmoplegia is a feature.
Sources: Expert list
Congenital ophthalmoplegia v0.55 MFF Zornitza Stark Marked gene: MFF as ready
Congenital ophthalmoplegia v0.55 MFF Zornitza Stark Gene: mff has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.55 MFF Zornitza Stark Classified gene: MFF as Green List (high evidence)
Congenital ophthalmoplegia v0.55 MFF Zornitza Stark Gene: mff has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.54 MFF Zornitza Stark gene: MFF was added
gene: MFF was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: MFF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MFF were set to 26783368
Phenotypes for gene: MFF were set to Encephalopathy due to defective mitochondrial and peroxisomal fission 2, MIM# 617086
Review for gene: MFF was set to GREEN
Added comment: Ophthalmoplegia is a feature along with severe hypotonia with inability to walk, microcephaly, and abnormal signals in the basal ganglia.
Sources: Expert list
Congenital ophthalmoplegia v0.53 MUSK Zornitza Stark Marked gene: MUSK as ready
Congenital ophthalmoplegia v0.53 MUSK Zornitza Stark Gene: musk has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.53 MUSK Zornitza Stark Classified gene: MUSK as Green List (high evidence)
Congenital ophthalmoplegia v0.53 MUSK Zornitza Stark Gene: musk has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.52 MUSK Zornitza Stark gene: MUSK was added
gene: MUSK was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: MUSK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MUSK were set to Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency, MIM# 616325
Review for gene: MUSK was set to GREEN
Added comment: Ophthalmoplegia is a feature.
Sources: Expert list
Congenital ophthalmoplegia v0.51 NDUFV1 Zornitza Stark Marked gene: NDUFV1 as ready
Congenital ophthalmoplegia v0.51 NDUFV1 Zornitza Stark Gene: ndufv1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.51 NDUFV1 Zornitza Stark Classified gene: NDUFV1 as Green List (high evidence)
Congenital ophthalmoplegia v0.51 NDUFV1 Zornitza Stark Gene: ndufv1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.50 NDUFV1 Zornitza Stark gene: NDUFV1 was added
gene: NDUFV1 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: NDUFV1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFV1 were set to Mitochondrial complex I deficiency, nuclear type 4, MIM# 618225
Review for gene: NDUFV1 was set to GREEN
Added comment: Ophthalmoplegia is a reported feature.
Sources: Expert list
Congenital ophthalmoplegia v0.49 MTM1 Zornitza Stark Marked gene: MTM1 as ready
Congenital ophthalmoplegia v0.49 MTM1 Zornitza Stark Gene: mtm1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.49 MTM1 Zornitza Stark Classified gene: MTM1 as Green List (high evidence)
Congenital ophthalmoplegia v0.49 MTM1 Zornitza Stark Gene: mtm1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.48 MTM1 Zornitza Stark gene: MTM1 was added
gene: MTM1 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: MTM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: MTM1 were set to Myotubular myopathy, X-linked, MIM# 310400
Review for gene: MTM1 was set to GREEN
Added comment: External ophthalmoplegia is a prominent feature.
Sources: Expert list
Congenital ophthalmoplegia v0.47 CHRNA1 Zornitza Stark Marked gene: CHRNA1 as ready
Congenital ophthalmoplegia v0.47 CHRNA1 Zornitza Stark Gene: chrna1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.47 CHRNA1 Zornitza Stark Classified gene: CHRNA1 as Green List (high evidence)
Congenital ophthalmoplegia v0.47 CHRNA1 Zornitza Stark Gene: chrna1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.46 CHRNA1 Zornitza Stark gene: CHRNA1 was added
gene: CHRNA1 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: CHRNA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CHRNA1 were set to Myasthenic syndrome, congenital, 1A, slow-channel, MIM# 601462
Review for gene: CHRNA1 was set to GREEN
Added comment: Ophthalmoplegia is a feature of this condition.
Sources: Expert list
Congenital ophthalmoplegia v0.45 CHAT Zornitza Stark Marked gene: CHAT as ready
Congenital ophthalmoplegia v0.45 CHAT Zornitza Stark Gene: chat has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.45 CHAT Zornitza Stark Classified gene: CHAT as Green List (high evidence)
Congenital ophthalmoplegia v0.45 CHAT Zornitza Stark Gene: chat has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.44 CHAT Zornitza Stark gene: CHAT was added
gene: CHAT was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: CHAT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CHAT were set to Myasthenic syndrome, congenital, 6, presynaptic, MIM# 254210
Review for gene: CHAT was set to GREEN
Added comment: Ophthalmoparesis and strabismus are a feature.
Sources: Expert list
Congenital ophthalmoplegia v0.43 OPA1 Zornitza Stark Marked gene: OPA1 as ready
Congenital ophthalmoplegia v0.43 OPA1 Zornitza Stark Gene: opa1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.43 OPA1 Zornitza Stark Classified gene: OPA1 as Green List (high evidence)
Congenital ophthalmoplegia v0.43 OPA1 Zornitza Stark Gene: opa1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.42 OPA1 Zornitza Stark gene: OPA1 was added
gene: OPA1 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: OPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: OPA1 were set to Optic atrophy plus syndrome, MIM# 125250
Review for gene: OPA1 was set to GREEN
Added comment: Childhood onset disorder, characterised by optic atrophy, but progressive external ophthalmoplegia can be a feature.
Sources: Expert list
Congenital ophthalmoplegia v0.41 PIEZO2 Zornitza Stark Marked gene: PIEZO2 as ready
Congenital ophthalmoplegia v0.41 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.41 PIEZO2 Zornitza Stark Classified gene: PIEZO2 as Green List (high evidence)
Congenital ophthalmoplegia v0.41 PIEZO2 Zornitza Stark Gene: piezo2 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.40 PIEZO2 Zornitza Stark gene: PIEZO2 was added
gene: PIEZO2 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: PIEZO2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PIEZO2 were set to Arthrogryposis, distal, type 5, MIM# 108145; Arthrogryposis, distal, type 3, MIM# 114300
Review for gene: PIEZO2 was set to GREEN
Added comment: Ophthalmoplegia is an associated feature.
Sources: Expert list
Congenital ophthalmoplegia v0.39 NDUFS1 Zornitza Stark Marked gene: NDUFS1 as ready
Congenital ophthalmoplegia v0.39 NDUFS1 Zornitza Stark Gene: ndufs1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.39 NDUFS1 Zornitza Stark Classified gene: NDUFS1 as Green List (high evidence)
Congenital ophthalmoplegia v0.39 NDUFS1 Zornitza Stark Gene: ndufs1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.38 NDUFS1 Zornitza Stark gene: NDUFS1 was added
gene: NDUFS1 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: NDUFS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NDUFS1 were set to Mitochondrial complex I deficiency, nuclear type 5, MIM# 618226
Review for gene: NDUFS1 was set to GREEN
Added comment: Nystagmus, strabismus and ophthalmoplegia are features.
Sources: Expert list
Congenital ophthalmoplegia v0.37 MGME1 Zornitza Stark Marked gene: MGME1 as ready
Congenital ophthalmoplegia v0.37 MGME1 Zornitza Stark Gene: mgme1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.37 MGME1 Zornitza Stark Classified gene: MGME1 as Green List (high evidence)
Congenital ophthalmoplegia v0.37 MGME1 Zornitza Stark Gene: mgme1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.36 MGME1 Zornitza Stark gene: MGME1 was added
gene: MGME1 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: MGME1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MGME1 were set to Mitochondrial DNA depletion syndrome 11, MIM#615084
Review for gene: MGME1 was set to GREEN
Added comment: Onset in the first decade, and progressive external ophthalmoplegia is a prominent feature.
Sources: Expert list
Congenital ophthalmoplegia v0.35 SLC9A6 Zornitza Stark Marked gene: SLC9A6 as ready
Congenital ophthalmoplegia v0.35 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.35 SLC9A6 Zornitza Stark Classified gene: SLC9A6 as Green List (high evidence)
Congenital ophthalmoplegia v0.35 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.34 SLC9A6 Zornitza Stark gene: SLC9A6 was added
gene: SLC9A6 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: SLC9A6 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: SLC9A6 were set to Mental retardation, X-linked syndromic, Christianson type, MIM# 300243
Review for gene: SLC9A6 was set to GREEN
Added comment: Impaired eye movements including ophthalmoplegia are a feature.
Sources: Expert list
Congenital ophthalmoplegia v0.33 PDHB Zornitza Stark Marked gene: PDHB as ready
Congenital ophthalmoplegia v0.33 PDHB Zornitza Stark Gene: pdhb has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.33 PDHB Zornitza Stark Classified gene: PDHB as Green List (high evidence)
Congenital ophthalmoplegia v0.33 PDHB Zornitza Stark Gene: pdhb has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.32 PDHB Zornitza Stark gene: PDHB was added
gene: PDHB was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: PDHB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PDHB were set to Pyruvate dehydrogenase E1-beta deficiency, MIM# 614111
Review for gene: PDHB was set to GREEN
Added comment: Well established gene disease association, strabismus and abnormal eye movements are a feature in addition to lactic acidosis and hypotonia.
Sources: Expert list
Congenital ophthalmoplegia v0.31 COLQ Zornitza Stark Marked gene: COLQ as ready
Congenital ophthalmoplegia v0.31 COLQ Zornitza Stark Gene: colq has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.31 COLQ Zornitza Stark Classified gene: COLQ as Green List (high evidence)
Congenital ophthalmoplegia v0.31 COLQ Zornitza Stark Gene: colq has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.30 COLQ Zornitza Stark gene: COLQ was added
gene: COLQ was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: COLQ was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COLQ were set to Myasthenic syndrome, congenital, 5, MIM# 603034
Review for gene: COLQ was set to GREEN
Added comment: Well established gene-disease association. Ophthalmoparesis is a feature.
Sources: Expert list
Congenital ophthalmoplegia v0.29 SLC19A3 Zornitza Stark Marked gene: SLC19A3 as ready
Congenital ophthalmoplegia v0.29 SLC19A3 Zornitza Stark Gene: slc19a3 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.29 SLC19A3 Zornitza Stark Classified gene: SLC19A3 as Green List (high evidence)
Congenital ophthalmoplegia v0.29 SLC19A3 Zornitza Stark Gene: slc19a3 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.28 SLC19A3 Zornitza Stark gene: SLC19A3 was added
gene: SLC19A3 was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: SLC19A3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC19A3 were set to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), MIM# 607483
Review for gene: SLC19A3 was set to GREEN
Added comment: Well established gene-disease association, treatable condition. External ophthalmoplegia is a feature.
Sources: Expert list
Congenital ophthalmoplegia v0.27 GBA Zornitza Stark Marked gene: GBA as ready
Congenital ophthalmoplegia v0.27 GBA Zornitza Stark Gene: gba has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.27 GBA Zornitza Stark Classified gene: GBA as Green List (high evidence)
Congenital ophthalmoplegia v0.27 GBA Zornitza Stark Gene: gba has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.26 GBA Zornitza Stark gene: GBA was added
gene: GBA was added to Congenital ophthalmoplegia. Sources: Expert list
Mode of inheritance for gene: GBA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GBA were set to Gaucher disease, type II, MIM# 230900
Review for gene: GBA was set to GREEN
Added comment: Well established gene-disease association. Cranial nerve involvement is common and can manifest as convergent squint, strabismus, ocular paresis, oculomotor apraxia.
Sources: Expert list
Congenital ophthalmoplegia v0.24 Zornitza Stark Panel name changed from Congenital fibrosis of the extraocular muscles to Congenital ophthalmoplegia
Congenital ophthalmoplegia v0.23 SALL4 Zornitza Stark Marked gene: SALL4 as ready
Congenital ophthalmoplegia v0.23 SALL4 Zornitza Stark Gene: sall4 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.23 SALL4 Zornitza Stark Classified gene: SALL4 as Green List (high evidence)
Congenital ophthalmoplegia v0.23 SALL4 Zornitza Stark Gene: sall4 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.22 ROBO3 Zornitza Stark Marked gene: ROBO3 as ready
Congenital ophthalmoplegia v0.22 ROBO3 Zornitza Stark Gene: robo3 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.22 ROBO3 Zornitza Stark Classified gene: ROBO3 as Green List (high evidence)
Congenital ophthalmoplegia v0.22 ROBO3 Zornitza Stark Gene: robo3 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.21 REV3L Zornitza Stark Marked gene: REV3L as ready
Congenital ophthalmoplegia v0.21 REV3L Zornitza Stark Gene: rev3l has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.21 REV3L Zornitza Stark Phenotypes for gene: REV3L were changed from möbius syndrome to Möbius syndrome
Congenital ophthalmoplegia v0.20 REV3L Zornitza Stark Classified gene: REV3L as Green List (high evidence)
Congenital ophthalmoplegia v0.20 REV3L Zornitza Stark Gene: rev3l has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.18 PLXND1 Zornitza Stark Marked gene: PLXND1 as ready
Congenital ophthalmoplegia v0.18 PLXND1 Zornitza Stark Gene: plxnd1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.18 PLXND1 Zornitza Stark Phenotypes for gene: PLXND1 were changed from möbius syndrome to Möbius syndrome
Congenital ophthalmoplegia v0.17 PLXND1 Zornitza Stark Classified gene: PLXND1 as Green List (high evidence)
Congenital ophthalmoplegia v0.17 PLXND1 Zornitza Stark Gene: plxnd1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.16 MYMK Zornitza Stark Marked gene: MYMK as ready
Congenital ophthalmoplegia v0.16 MYMK Zornitza Stark Gene: mymk has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.16 MYMK Zornitza Stark Tag founder tag was added to gene: MYMK.
Congenital ophthalmoplegia v0.16 MYMK Zornitza Stark Publications for gene: MYMK were set to PMID: 28681861
Congenital ophthalmoplegia v0.15 MYMK Zornitza Stark Classified gene: MYMK as Green List (high evidence)
Congenital ophthalmoplegia v0.15 MYMK Zornitza Stark Gene: mymk has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.14 MYMK Zornitza Stark reviewed gene: MYMK: Rating: GREEN; Mode of pathogenicity: None; Publications: 29560417; Phenotypes: Carey-Fineman-Ziter syndrome, MIM# 254940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.13 HOXA1 Zornitza Stark Marked gene: HOXA1 as ready
Congenital ophthalmoplegia v0.13 HOXA1 Zornitza Stark Gene: hoxa1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.13 HOXA1 Zornitza Stark Classified gene: HOXA1 as Green List (high evidence)
Congenital ophthalmoplegia v0.13 HOXA1 Zornitza Stark Gene: hoxa1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.11 ECEL1 Zornitza Stark Marked gene: ECEL1 as ready
Congenital ophthalmoplegia v0.11 ECEL1 Zornitza Stark Gene: ecel1 has been classified as Amber List (Moderate Evidence).
Congenital ophthalmoplegia v0.11 ECEL1 Zornitza Stark Classified gene: ECEL1 as Amber List (moderate evidence)
Congenital ophthalmoplegia v0.11 ECEL1 Zornitza Stark Gene: ecel1 has been classified as Amber List (Moderate Evidence).
Congenital ophthalmoplegia v0.10 GRHL2 Zornitza Stark Marked gene: GRHL2 as ready
Congenital ophthalmoplegia v0.10 GRHL2 Zornitza Stark Gene: grhl2 has been classified as Red List (Low Evidence).
Congenital ophthalmoplegia v0.10 GRHL2 Zornitza Stark Tag SV/CNV tag was added to gene: GRHL2.
Congenital ophthalmoplegia v0.10 CHN1 Zornitza Stark Marked gene: CHN1 as ready
Congenital ophthalmoplegia v0.10 CHN1 Zornitza Stark Gene: chn1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.10 CHN1 Zornitza Stark Classified gene: CHN1 as Green List (high evidence)
Congenital ophthalmoplegia v0.10 CHN1 Zornitza Stark Gene: chn1 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.9 TUBB2B Zornitza Stark Marked gene: TUBB2B as ready
Congenital ophthalmoplegia v0.9 TUBB2B Zornitza Stark Gene: tubb2b has been classified as Red List (Low Evidence).
Congenital ophthalmoplegia v0.9 TUBB2B Zornitza Stark Publications for gene: TUBB2B were set to 23001566
Congenital ophthalmoplegia v0.8 TUBB2B Zornitza Stark reviewed gene: TUBB2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital ophthalmoplegia v0.8 REV3L Shannon LeBlanc gene: REV3L was added
gene: REV3L was added to Congenital fibrosis of the extraocular muscles. Sources: Literature
Mode of inheritance for gene: REV3L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: REV3L were set to PMID: 26068067
Phenotypes for gene: REV3L were set to möbius syndrome
Review for gene: REV3L was set to GREEN
Added comment: de novo variants in 3 unrelated individuals with möbius syndrome and some functional evidence
Sources: Literature
Congenital ophthalmoplegia v0.8 PLXND1 Shannon LeBlanc gene: PLXND1 was added
gene: PLXND1 was added to Congenital fibrosis of the extraocular muscles. Sources: Literature
Mode of inheritance for gene: PLXND1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLXND1 were set to PMID: 26068067
Phenotypes for gene: PLXND1 were set to möbius syndrome
Review for gene: PLXND1 was set to GREEN
Added comment: PMID 26068067 : de novo mutations in 3 unrelated patients with moebius syndrome with some functional evidence.
Sources: Literature
Congenital ophthalmoplegia v0.8 MYMK Shannon LeBlanc gene: MYMK was added
gene: MYMK was added to Congenital fibrosis of the extraocular muscles. Sources: Other
Mode of inheritance for gene: MYMK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYMK were set to PMID: 28681861
Phenotypes for gene: MYMK were set to Carey-Fineman-Ziter syndrome, MIM 254940
Review for gene: MYMK was set to GREEN
Added comment: Congenital myopathy due to defect in myoblast fusion. Moebius syndrome / ophthalmoplegia is a common feature.
Sources: Other
Congenital ophthalmoplegia v0.8 ROBO3 Shannon LeBlanc gene: ROBO3 was added
gene: ROBO3 was added to Congenital fibrosis of the extraocular muscles. Sources: Literature
Mode of inheritance for gene: ROBO3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ROBO3 were set to PMID: 15105459; 16525029
Phenotypes for gene: ROBO3 were set to Gaze palsy, familial horizontal, with progressive scoliosis, 1 (MIM#607313)
Review for gene: ROBO3 was set to GREEN
Added comment: PMID 15105459: 10 patients with homozygous variants (1 nonsense, 1 splice site, 2 frameshift, and 6 missense mutations)

PMID 16525029 - 2 unrelated children with sporadic HGPPS: one patient compound het for 2 different 2-bp deletions, one patient compound het for a missense and a nonsense mutation.
Sources: Literature
Congenital ophthalmoplegia v0.8 HOXA1 Shannon LeBlanc gene: HOXA1 was added
gene: HOXA1 was added to Congenital fibrosis of the extraocular muscles. Sources: Literature
Mode of inheritance for gene: HOXA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HOXA1 were set to 17875913; 20227628; 18412118
Phenotypes for gene: HOXA1 were set to Athabaskan brainstem dysgenesis syndrome; Bosley-Salih-Alorainy syndrome - 601536
Review for gene: HOXA1 was set to GREEN
Added comment: The HOXA1-related syndrome phenotype is variable. The most common features in affected individuals are limited horizontal gaze (diagnosed as Duane syndrome in BSAS and horizontal gaze palsy in ABDS patients) and sensorineural deafness; facial weakness, mental retardation, autism, motor disabilities, central hypoventilation, carotid artery and/or conotruncal heart defects also occur (PMID 20227628)
Sources: Literature
Congenital ophthalmoplegia v0.8 CHN1 Shannon LeBlanc gene: CHN1 was added
gene: CHN1 was added to Congenital fibrosis of the extraocular muscles. Sources: Literature
Mode of inheritance for gene: CHN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHN1 were set to PMID 33004823; 18653847; 21555619
Phenotypes for gene: CHN1 were set to Duane retraction syndrome 2, 604356
Review for gene: CHN1 was set to GREEN
Added comment: Gain-of function aetiology: PMID 18653847 - in vitro evidence that gain-of-function heterozygous missense CHN1 mutations in patients with Duane retraction syndrome increase α2-chimaerin RacGAP activity; 21555619 - separate CHN1 mutations 2 families predicted to result in its hyperactivation.
Sources: Literature
Congenital ophthalmoplegia v0.8 SALL4 Shannon LeBlanc gene: SALL4 was added
gene: SALL4 was added to Congenital fibrosis of the extraocular muscles. Sources: Literature
Mode of inheritance for gene: SALL4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SALL4 were set to Duane-radial ray syndrome, 607323
Review for gene: SALL4 was set to GREEN
Added comment: well documented association with Duane-radial ray syndrome.
Sources: Literature
Congenital ophthalmoplegia v0.8 ECEL1 Shannon LeBlanc gene: ECEL1 was added
gene: ECEL1 was added to Congenital fibrosis of the extraocular muscles. Sources: Literature
Mode of inheritance for gene: ECEL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ECEL1 were set to PMID: 25173900
Phenotypes for gene: ECEL1 were set to Arthrogryposis, distal, type 5D - 615065; Congenital cranial dysinnervation disorder
Review for gene: ECEL1 was set to AMBER
Added comment: 25173900 described an ocular phenotype consistent with congenital cranial dysinnervation disorder (CCDD) in 3 of 4 siblings with ECEL-1 related distal arthrogryposis. The fourth affected sibling (with the mildest arthrogryposis in the family) had no ocular phenotype. Of 26 other reported recessive ECEL1 mutation cases (14 families), all had arthrogryposis, 19 had documented ptosis, and 4 had documented complex strabismus. One of these cases had both documented ptosis and complex strabismus.
Sources: Literature
Congenital ophthalmoplegia v0.8 GRHL2 Shannon LeBlanc reviewed gene: GRHL2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29110737; Phenotypes: Deafness, autosomal dominant 28, Corneal dystrophy, posterior polymorphous, 4; Mode of inheritance: None
Congenital ophthalmoplegia v0.8 TUBB2B Shannon LeBlanc reviewed gene: TUBB2B: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 11425694, 23001566; Phenotypes: Cortical dysplasia, complex, with other brain malformations 7, Fibrosis of extraocular muscles, congenital; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital ophthalmoplegia v0.8 COL25A1 Zornitza Stark Marked gene: COL25A1 as ready
Congenital ophthalmoplegia v0.8 COL25A1 Zornitza Stark Gene: col25a1 has been classified as Amber List (Moderate Evidence).
Congenital ophthalmoplegia v0.8 COL25A1 Zornitza Stark Phenotypes for gene: COL25A1 were changed from Fibrosis of extraocular muscles, congenital, 5; Fibrosis of extraocular muscles, congenital, 5 616219 to Fibrosis of extraocular muscles, congenital, 5, MIM# 616219
Congenital ophthalmoplegia v0.7 COL25A1 Zornitza Stark Publications for gene: COL25A1 were set to 25500261
Congenital ophthalmoplegia v0.6 KIF21A Zornitza Stark Marked gene: KIF21A as ready
Congenital ophthalmoplegia v0.6 KIF21A Zornitza Stark Gene: kif21a has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.6 KIF21A Zornitza Stark Phenotypes for gene: KIF21A were changed from Fibrosis of extraocular muscles, congenital, 1, MIM# 135700 to Fibrosis of extraocular muscles, congenital, 1/3B, MIM# 135700
Congenital ophthalmoplegia v0.5 KIF21A Zornitza Stark Phenotypes for gene: KIF21A were changed from Fibrosis of extraocular muscles, congenital, 1 135700; Congenital fibrosis of the extraocular muscles; Fibrosis of extraocular muscles, congenital, 3B 135700 to Fibrosis of extraocular muscles, congenital, 1, MIM# 135700
Congenital ophthalmoplegia v0.4 KIF21A Zornitza Stark Publications for gene: KIF21A were set to 15621876; 15223798; 15621877; 18332320
Congenital ophthalmoplegia v0.3 PHOX2A Zornitza Stark Marked gene: PHOX2A as ready
Congenital ophthalmoplegia v0.3 PHOX2A Zornitza Stark Gene: phox2a has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.3 PHOX2A Zornitza Stark Phenotypes for gene: PHOX2A were changed from Fibrosis of extraocular muscles, congenital, 2 602078; Fibrosis of extraocular muscles, congenital, 2 to Fibrosis of extraocular muscles, congenital, 2, MIM# 602078
Congenital ophthalmoplegia v0.2 PHOX2A Zornitza Stark Publications for gene: PHOX2A were set to 14597037; 22311481; 11600883
Congenital ophthalmoplegia v0.1 TUBB3 Zornitza Stark Marked gene: TUBB3 as ready
Congenital ophthalmoplegia v0.1 TUBB3 Zornitza Stark Gene: tubb3 has been classified as Green List (High Evidence).
Congenital ophthalmoplegia v0.1 TUBB3 Zornitza Stark Publications for gene: TUBB3 were set to 27428177; 20074521
Congenital ophthalmoplegia v0.0 TUBB3 Zornitza Stark reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fibrosis of extraocular muscles, congenital, 3A, MIM# 600638; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital ophthalmoplegia v0.0 COL25A1 Shannon LeBlanc reviewed gene: COL25A1: Rating: AMBER; Mode of pathogenicity: None; Publications: OMID: 25500261, 26486031; Phenotypes: Fibrosis of extraocular muscles, congenital, 5, 610004; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.0 PHOX2A Shannon LeBlanc reviewed gene: PHOX2A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11600883, 14597037, 16815872; Phenotypes: Fibrosis of extraocular muscles, congenital, 2, 602078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital ophthalmoplegia v0.0 KIF21A Shannon LeBlanc reviewed gene: KIF21A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 14595441, 28930843, 27513105, 26190014, 24656932; Phenotypes: Fibrosis of extraocular muscles, congenital, 1, 135700, Fibrosis of extraocular muscles, congenital, 3B, 135700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital ophthalmoplegia v0.0 TUBB3 Shannon LeBlanc reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:27428177, 20074521, 26639658; Phenotypes: Fibrosis of extraocular muscles, congenital, 3A 600638, Cortical dysplasia, complex, with other brain malformations 1, 602661; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital ophthalmoplegia v0.0 TUBB2B Zornitza Stark gene: TUBB2B was added
gene: TUBB2B was added to Congenital fibrosis of the extraocular muscles. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: TUBB2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB2B were set to 23001566
Phenotypes for gene: TUBB2B were set to Fibrosis of extraocular muscles, congenital; Cortical dysplasia, complex, with other brain malformations 7
Congenital ophthalmoplegia v0.0 GRHL2 Zornitza Stark gene: GRHL2 was added
gene: GRHL2 was added to Congenital fibrosis of the extraocular muscles. Sources: Genomics England PanelApp,Expert Review Red
Mode of inheritance for gene: GRHL2 was set to Unknown
Publications for gene: GRHL2 were set to 29110737
Phenotypes for gene: GRHL2 were set to Fibrosis of extraocular muscles, congenital
Congenital ophthalmoplegia v0.0 COL25A1 Zornitza Stark gene: COL25A1 was added
gene: COL25A1 was added to Congenital fibrosis of the extraocular muscles. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: COL25A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL25A1 were set to 25500261
Phenotypes for gene: COL25A1 were set to Fibrosis of extraocular muscles, congenital, 5; Fibrosis of extraocular muscles, congenital, 5 616219
Congenital ophthalmoplegia v0.0 TUBB3 Zornitza Stark gene: TUBB3 was added
gene: TUBB3 was added to Congenital fibrosis of the extraocular muscles. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: TUBB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB3 were set to 27428177; 20074521
Phenotypes for gene: TUBB3 were set to Fibrosis of extraocular muscles, congenital, 3A 600638; CFEOM3A
Congenital ophthalmoplegia v0.0 PHOX2A Zornitza Stark gene: PHOX2A was added
gene: PHOX2A was added to Congenital fibrosis of the extraocular muscles. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: PHOX2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHOX2A were set to 14597037; 22311481; 11600883
Phenotypes for gene: PHOX2A were set to Fibrosis of extraocular muscles, congenital, 2 602078; Fibrosis of extraocular muscles, congenital, 2
Congenital ophthalmoplegia v0.0 KIF21A Zornitza Stark gene: KIF21A was added
gene: KIF21A was added to Congenital fibrosis of the extraocular muscles. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: KIF21A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF21A were set to 15621876; 15223798; 15621877; 18332320
Phenotypes for gene: KIF21A were set to Fibrosis of extraocular muscles, congenital, 1 135700; Congenital fibrosis of the extraocular muscles; Fibrosis of extraocular muscles, congenital, 3B 135700
Congenital ophthalmoplegia v0.0 Zornitza Stark Added panel Congenital fibrosis of the extraocular muscles