Heterozygous Nonsense Variants in the Ferritin Heavy Chain Gene FTH1 Cause a Neuroferritinopathy.

ABSTRACT: Ferritin, the iron storage protein, is composed of light and heavy chain subunits, encoded by FTL and FTH1, respectively. Heterozygous variants in FTL cause hereditary neuroferritinopathy, a type of neurodegeneration with brain iron accumulation (NBIA). Variants in FTH1 have not been previously associated with neurologic disease. We describe the clinical, neuroimaging, and neuropathology findings of five unrelated pediatric patients with de novo heterozygous FTH1 variants. Children presented with developmental delay, epilepsy, and progressive neurologic decline. Nonsense FTH1 variants were identified using whole exome sequencing, with a recurrent variant (p.Phe171*) identified in four unrelated individuals. Neuroimaging revealed diffuse volume loss, features of pontocerebellar hypoplasia a

SUBMITTER: Shieh JT 

PROVIDER: S-EPMC10510067 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature