Reduced gene dosage is a common mechanism of neuropathologies caused by ATP6AP2 splicing mutations.

ABSTRACT:

Background

Mutations that alter splicing of X-linked ATP6AP2 cause a spectrum of neurodevelopmental and neurodegenerative pathologies including parkinsonism in affected males. All previously reported splicing mutations increase the level of a minor isoform with skipped exon 4 (Δe4) that encodes a functionally deficient protein.

Objectives

We investigated the pathogenic mechanism of a novel c.168+6T>A variant reported in a family with X-linked intellectual disability, epilepsy, and parkinsonism. We also analyzed ATP6AP2 splicing defects in brains of carriers of a c.345C>T variant associated with X-linked spasticity and parkinsonism.

Methods

We generated induced pluripotent stem cells from patients with c.168+6T>A, reprogrammed them to neural progenitor cells and analyz

SUBMITTER: Edelman WC 

PROVIDER: S-EPMC10012809 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature