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

doi:10.1093/hmg/ddt380

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Congenital myopathy is caused by mutation of HACD1

Journal article

Open access

Peer reviewed

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, …

Human molecular genetics, Vol.22(25), pp.5229-5236

12/20/2013

DOI: 10.1093/hmg/ddt380

PMCID: PMC3842179

PMID: 23933735

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Abstract

Congenital myopathies are heterogeneous inherited diseases of muscle 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 with congenital myopathy in humans. We suggest that the mutation in the HACD1 gene causes 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.

Amino Acid Sequence

Myopathies, Structural, Congenital - physiopathology

Humans

Child, Preschool

Infant

Male

Myopathies, Structural, Congenital - genetics

Protein Tyrosine Phosphatases - metabolism

RNA Stability - genetics

Homozygote

Exome - genetics

Protein Tyrosine Phosphatases - genetics

Muscular Diseases - physiopathology

Pedigree

Adolescent

Adult

Female

Consanguinity

High-Throughput Nucleotide Sequencing

Muscular Diseases - genetics

Mutation

Child

Fatty Acids - metabolism

Genetic Linkage

Details

Title: Subtitle: Congenital myopathy is caused by mutation of HACD1
Creators: Emad Muhammad - Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences and
Orit Reish
Yusuke Ohno
Todd Scheetz
Adam Deluca
Charles Searby
Miriam Regev
Lilach Benyamini
Yakov Fellig
Akio Kihara
Val C Sheffield
Ruti Parvari
Resource Type: Journal article
Publication Details: Human molecular genetics, Vol.22(25), pp.5229-5236
DOI: 10.1093/hmg/ddt380
PMID: 23933735
PMCID: PMC3842179
NLM abbreviation: Hum Mol Genet
ISSN: 0964-6906
eISSN: 1460-2083
Publisher: England
Grant note: Howard Hughes Medical Institute
Language: English
Date published: 12/20/2013
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Center for Bioinformatics and Computational Biology; Ophthalmology and Visual Sciences
Record Identifier: 9983979957402771

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