Autosomal recessive lethal congenital contractural syndrome type 4 (LCCS4) caused by a mutation in MYBPC1

Authors

  • Barak Markus,

    1. The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev, Ben Gurion University, Beer-Sheva, Israel
    2. Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel
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    • These authors contributed equally to this work.

  • Ginat Narkis,

    1. The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev, Ben Gurion University, Beer-Sheva, Israel
    2. Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel
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    • These authors contributed equally to this work.

  • Daniella Landau,

    1. Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel
    2. Division of Pediatrics, Soroka Medical Center, Beer-Sheva, Israel
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  • Ruth Z. Birk,

    1. Ariel University Center, Ariel, Israel
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  • Idan Cohen,

    1. The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev, Ben Gurion University, Beer-Sheva, Israel
    2. Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel
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  • Ohad S. Birk

    Corresponding author
    1. The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev, Ben Gurion University, Beer-Sheva, Israel
    2. Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel
    3. Genetics Institute, Soroka Medical Center, Beer-Sheva, Israel
    • Genetics Institute, Soroka Medical Center, P.O. Box 151, Beer-Sheva 84101, Israel.
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  • Communicated by Hamish S. Scott

Abstract

Autosomal recessive lethal congenital contractural syndrome (LCCS) is a severe form of neuromuscular arthrogryposis. We previously showed that this phenotype is caused in two unrelated inbred Bedouin tribes by different defects in the phosphatidylinositol pathway. However, the molecular basis of the same phenotype in other tribes remained elusive. Whole exome sequencing identified a novel LCCS founder mutation within a minimal shared homozygosity locus of approximately 1 Mb in two affected individuals of different tribes: a homozygous premature stop producing mutation in MYBPC1, encoding myosin-binding protein C, slow type. A dominant missense mutation in MYBPC1 was previously shown to cause mild distal arthrogryposis. We now show that a recessive mutation abrogating all functional domains in the same gene leads to LCCS. Hum Mutat 33:1435–1438, 2012. © 2012 Wiley Periodicals, Inc.

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