Novel, complex configurations of the <i>MARCHF6</i> repeat expansion associated with progressive myoclonic epilepsy and familial adult myoclonic epilepsy.

ABSTRACT: Repeat expansions are a known cause of progressive myoclonic epilepsy (PME) and familial adult myoclonic epilepsy (FAME). We hypothesized that PME and FAME may have an overlapping phenotypic spectrum and searched for pathogenic repeat expansions in 18 individuals from 15 families with later-onset PME or FAME. We generated whole genome sequencing data by short-read sequencing and searched for known and novel repeat expansions. No known, pathogenic repeat expansions were identified. Instead, we discovered a novel TTGTA expansion in the gene MARCHF6 at the same location as the known, pathogenic FAME3 expansion in a PME family. Targeted long-read sequencing of this locus revealed a large, complex repeat structure harbouring an expansion of the pathogenic TTTCA repeat that causes FAME, s

SUBMITTER: Bennett MF 

PROVIDER: S-EPMC12628750 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature