KCTD7 deficiency defines a distinct neurodegenerative disorder with a conserved autophagy-lysosome defect.

ABSTRACT:

Objective

Several small case series identified KCTD7 mutations in patients with a rare autosomal recessive disorder designated progressive myoclonic epilepsy (EPM3) and neuronal ceroid lipofuscinosis (CLN14). Despite the name KCTD (potassium channel tetramerization domain), KCTD protein family members lack predicted channel domains. We sought to translate insight gained from yeast studies to uncover disease mechanisms associated with deficiencies in KCTD7 of unknown function.

Methods

Novel KCTD7 variants in new and published patients were assessed for disease causality using genetic analyses, cell-based functional assays of patient fibroblasts and knockout yeast, and electron microscopy of patient samples.

Results

Patients with KCTD7 mutations can exhibit movement dis

SUBMITTER: Metz KA 

PROVIDER: S-EPMC6295419 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature