Regression
Gene: FTH1EnsemblGeneIds (GRCh38): ENSG00000167996
EnsemblGeneIds (GRCh37): ENSG00000167996
OMIM: 134770, Gene2Phenotype
FTH1 is in 5 panels
3 reviews
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Neurodegeneration with brain iron accumulation 9, MIM# 620669
Bryony Thompson (Royal Melbourne Hospital)
Comment on list classification: Article describing the gene-disease association with neuroferritinopathy now published in HGG advancesCreated: 4 Sep 2023, 10:44 p.m. | Last Modified: 4 Sep 2023, 10:44 p.m.
Panel Version: 0.532
Paul De Fazio (Victorian Clinical Genetics Services)
Note paper is pre-print hence Amber rating.
5 unrelated paediatric patients presented with developmental delay, epilepsy, and progressive neurologic decline. Heterozygous nonsense FTH1 variants were identified by WES in all patients, 4 of which were confirmed de novo. All variants are predicted to escape NMD and appear to act by a dominant toxic gain-of-function mechanism. p.F171* was recurrent in three unrelated individuals.
Patient fibroblasts show elevated ferritin protein levels, markers of oxidative stress, and increased susceptibility to iron accumulation. Targeted knock-down of mutant FTH1 transcript with rescues cellular phenotypes.
Note NMD-escape variants in gnomAD exist, upstream of the variants in patients.
Sources: LiteratureCreated: 2 Mar 2023, 3:57 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Neuroferritinopathy (MONDO:0011638)
Publications
Mode of pathogenicity
Other
Variants in this GENE are reported as part of current diagnostic practice
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
- Sources
-
- Expert Review Green
- Phenotypes
-
- Neurodegeneration with brain iron accumulation 9, MIM# 620669
- OMIM
- 134770
- Clinvar variants
- Variants in FTH1
- Penetrance
- None
- Publications
- Mode of Pathogenicity
- Other
- Panels with this gene
History Filter Activity
Set Phenotypes
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Phenotypes for gene: FTH1 were changed from Neuroferritinopathy (MONDO:0011638) to Neurodegeneration with brain iron accumulation 9, MIM# 620669
Set publications
Bryony Thompson (Royal Melbourne Hospital)Publications for gene: FTH1 were set to 36778397
Entity classified by Genomics England curator
Bryony Thompson (Royal Melbourne Hospital)Gene: fth1 has been classified as Green List (High Evidence).
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: fth1 has been classified as Amber List (Moderate Evidence).
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: fth1 has been classified as Amber List (Moderate Evidence).
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set mode of pathogenicity
Paul De Fazio (Victorian Clinical Genetics Services)gene: FTH1 was added gene: FTH1 was added to Regression. Sources: Literature Mode of inheritance for gene: FTH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: FTH1 were set to 36778397 Phenotypes for gene: FTH1 were set to Neuroferritinopathy (MONDO:0011638) Mode of pathogenicity for gene: FTH1 was set to Other Review for gene: FTH1 was set to AMBER gene: FTH1 was marked as current diagnostic