Gain-of-function variants in CLCN7 cause hypopigmentation and lysosomal storage disease.

ABSTRACT: Together with its β-subunit OSTM1, ClC-7 performs 2Cl^-/H⁺ exchange across lysosomal membranes. Pathogenic variants in either gene cause lysosome-related pathologies, including osteopetrosis and lysosomal storage. CLCN7 variants can cause recessive or dominant disease. Different variants entail different sets of symptoms. Loss of ClC-7 causes osteopetrosis and mostly neuronal lysosomal storage. A recently reported de novo CLCN7 mutation (p.Tyr715Cys) causes widespread severe lysosome pathology (hypopigmentation, organomegaly, and delayed myelination and development, "HOD syndrome"), but no osteopetrosis. We now describe two additional HOD individuals with the previously described p.Tyr715Cys and a novel p.Lys285Thr mutation, respectively. Both mutations decreased ClC-7

SUBMITTER: Polovitskaya MM 

PROVIDER: S-EPMC11261146 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature