Bi-allelic mutations in MYL1 cause a severe congenital myopathy

Ravenscroft G., Zaharieva I. T., Bortolotti C. A., Lambrughi M., Pignataro M., Borsari M., ...More

HUMAN MOLECULAR GENETICS, vol.27, no.24, pp.4263-4272, 2018 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 27 Issue: 24
  • Publication Date: 2018
  • Doi Number: 10.1093/hmg/ddy320
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.4263-4272
  • Hacettepe University Affiliated: Yes


Congenital myopathies are typically characterised by early onset hypotonia, weakness and hallmark features on biopsy. Despite the rapid pace of gene discovery, similar to 50% of patients with a congenital myopathy remain without a genetic diagnosis following screening of known disease genes. We performed exome sequencing on two consanguineous probands diagnosed with a congenital myopathy and muscle biopsy showing selective atrophy/hypotrophy or absence of type II myofibres. We identified variants in the gene (MYL1) encoding the skeletal muscle fast-twitch specific myosin essential light chain (ELC) in both probands. A homozygous essential splice acceptor variant (c.479-2A> G, predicted to result in skipping of exon 5 was identified in Proband 1, and a homozygous missense substitution (c.488T>G, p.(Met163Arg)) was identified in Proband 2. Protein modelling of the p.(Met163Arg) substitution predicted it might impede intermolecular interactions that facilitate