The M694V mutation in Armenian-Americans: a 10-year retrospective study of MEFV mutation testing for familial Mediterranean fever at UCLA

Authors

  • FS Ong,

    1. Department of Biomedical Sciences
    2. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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    • These authors equally contributed.

  • H Vakil,

    1. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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    • These authors equally contributed.

  • Y Xue,

    1. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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    • These authors equally contributed.

  • JZ Kuo,

    1. Department of Biomedical Sciences
    2. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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  • KH Shah,

    1. Department of Biomedical Sciences
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  • RB Lee,

    1. Department of Biomedical Sciences
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  • KE Bernstein,

    1. Department of Biomedical Sciences
    2. Department of Pathology and Laboratory Medicine
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  • DL Rimoin,

    1. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
    2. Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
    3. Department of Medicine
    4. Department of Pediatrics
    5. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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  • T Getzug,

    1. Department of Medicine
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  • K Das,

    1. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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  • JL Deignan,

    1. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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  • JI Rotter,

    1. Department of Biomedical Sciences
    2. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
    3. Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
    4. Department of Medicine
    5. Department of Pediatrics
    6. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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  • WW Grody

    Corresponding author
    1. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
    2. Department of Pediatrics
    3. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
    • Department of Biomedical Sciences
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  • Each author declares no conflict of interest.

Corresponding author: Wayne W. Grody, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, Los Angeles, CA 90095, USA.

Tel.: +310 825 5648;

fax: +310 206 4255;

e-mail: wgrody@mednet.ucla.edu

Abstract

Familial Mediterranean fever (FMF), inherited in an autosomal recessive manner, is a systemic auto-inflammatory disorder characterized by recurrent attacks of fever with peritonitis, pleuritis, synovitis and erysipeloid rash. The marenostrin-encoding fever (MEFV) gene, located on chromosome 16p13.3, is the only gene in which mutations are currently known to cause FMF. To correlate specific genotypes with adverse phenotypes of affected populations residing in the Western United States, a retrospective case series review was conducted of all MEFV gene mutation testing completed at UCLA Clinical Molecular Diagnostic Laboratory between February 2002 and February 2012, followed by clinical chart review of all subjects who either have a single or double mutation. All 12 common mutations in the MEFV gene were analyzed and the M694V variant was found to be associated with an adverse FMF clinical outcome in the Armenian-American population, manifested by earlier onset of disease, increased severity of disease, and renal amyloidosis.

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