Congenital myopathy is caused by mutation of HACD1

Emad Muhammad, Orit Reish, Yusuke Ohno, Todd Scheetz, Adam DeLuca, Charles Searby, Miriam Regev, Lilach Benyamini, Yakov Fellig, Akio Kihara, Val C. Sheffield, Ruti Parvari

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Congenital myopathies are heterogeneous inherited diseases ofmuscle characterized by a range of distinctive histologic abnormalities. We have studied a consanguineous family with congenital myopathy. Genome-wide linkage analysis and whole-exome sequencing identified a homozygous non-sense mutation in 3-hydroxyacyl- CoA dehydratase 1 (HACD1) in affected individuals. The mutation results in non-sense mediated decay of the HACD1 mRNA to 31% of control levels in patient muscle and completely abrogates the enzymatic activity of dehydration of 3-hydroxyacyl-CoA, the third step in the elongation of very long-chain fatty acids (VLCFAs). We describe clinical findings correlated with a deleterious mutation in a gene not previously known to be associated withcongenitalmyopathy inhumans. Wesuggest that the mutation in theHACD1genecauses a reduction in the synthesis of VLCFAs, which are components of membrane lipids and participants in physiological processes, leading to congenital myopathy. These data indicate that HACD1 is necessary for muscle function.

Original languageEnglish
Article numberddt380
Pages (from-to)5229-5236
Number of pages8
JournalHuman Molecular Genetics
Issue number25
StatePublished - 1 Dec 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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