A Recurrent Gain-of-Function Mutation in CLCN6, Encoding the ClC-6 Cl^-/H⁺-Exchanger, Causes Early-Onset Neurodegeneration.

ABSTRACT: Dysfunction of the endolysosomal system is often associated with neurodegenerative disease because postmitotic neurons are particularly reliant on the elimination of intracellular aggregates. Adequate function of endosomes and lysosomes requires finely tuned luminal ion homeostasis and transmembrane ion fluxes. Endolysosomal CLC Cl^-/H⁺ exchangers function as electric shunts for proton pumping and in luminal Cl^- accumulation. We now report three unrelated children with severe neurodegenerative disease, who carry the same de novo c.1658A>G (p.Tyr553Cys) mutation in CLCN6, encoding the late endosomal Cl^-/H⁺-exchanger ClC-6. Whereas Clcn6^-/- mice have only mild neuronal lysosomal storage abnormalities, the affected individuals d

SUBMITTER: Polovitskaya MM 

PROVIDER: S-EPMC7820737 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature