Progressive myoclonus epilepsy caused by a homozygous splicing variant of SLC7A6OS.

Abstract

Exome sequencing was performed in two unrelated families with progressive myoclonus epilepsy. Affected individuals from both families shared a rare, homozygous c.191A>G variant affecting a splice site in SLC7A6OS. Analysis of cDNA from lymphoblastoid cells demonstrated partial splice site abolition and the creation of an abnormal isoform. RT-qPCR and western blot showed a marked reduction of protein expression. Haplotype analysis identified a ~0.85cM shared genomic region on chromosome 16q encompassing the c.191A>G variant, consistent with a distant ancestor common to both families. Our results suggest that bi-allelic loss-of-function variants in SLC7A6OS are a novel genetic cause of progressive myoclonus epilepsy. This article is protected by copyright. All rights reserved.