Regression
Gene: FTH1
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Neurodegeneration with brain iron accumulation 9, MIM# 620669
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
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
Phenotypes for gene: FTH1 were changed from Neuroferritinopathy (MONDO:0011638) to Neurodegeneration with brain iron accumulation 9, MIM# 620669
Publications for gene: FTH1 were set to 36778397
Gene: fth1 has been classified as Green List (High Evidence).
Gene: fth1 has been classified as Amber List (Moderate Evidence).
Gene: fth1 has been classified as Amber List (Moderate Evidence).
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