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Maternal uniparental disomy of chromosome 4 in a patient with limb-girdle muscular dystrophy 2E confirmed by SNP array technology

Authors

  • CE Cottrell,

    1. Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA
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  • J Mendell,

    1. Department of Pathology
    2. Department of Pediatrics, The Ohio State University, Columbus, OH, USA
    3. Section of Neurology
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  • M Hart-Kothari,

    1. Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA
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  • D Ell,

    1. Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA
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  • DL Thrush,

    1. Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA
    2. Department of Pediatrics, The Ohio State University, Columbus, OH, USA
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  • C Astbury,

    1. Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA
    2. Department of Pathology
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  • M Pastore,

    1. Department of Pediatrics, The Ohio State University, Columbus, OH, USA
    2. Section of Molecular and Human Genetics, Nationwide Children's Hospital, Columbus, OH, USA
    3. Division of Molecular and Human Genetics, Department of Pediatrics, The Ohio State University, Columbus, OH, USA
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  • JM Gastier-Foster,

    1. Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA
    2. Department of Pathology
    3. Department of Pediatrics, The Ohio State University, Columbus, OH, USA
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  • RE Pyatt

    Corresponding author
    1. Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA
    2. Department of Pathology
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Dr Robert Pyatt, Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, 700 Children's Drive, C0986 Columbus, OH 43205, USA.
Tel.: +1 614-722-2866;
fax: +1 614-722-2887;
e-mail: Robert.Pyatt@NationwideChildrens.org

Abstract

Cottrell CE, Mendell J, Hart-Kothari M, Ell D, Thrush DL, Astbury C, Pastore M, Gastier-Foster JM, Pyatt RE. Maternal uniparental disomy of chromosome 4 in a patient with limb-girdle muscular dystrophy 2E confirmed by SNP array technology.

The limb-girdle muscular dystrophies (LGMDs) are a heterogenous group of diseases characterized by shoulder-girdle and pelvic muscle weakness and wasting. LGMD 2E is an autosomal recessively inherited form of the disease caused by mutations in the β-sarcoglycan (SGCB) gene located at 4q12. In this report, we describe a patient who demonstrates non-Mendelian inheritance of a homozygous missense mutation in SGCB resulting in disease expression. A combination of single-nucleotide polymorphism (SNP) array technology and microsatellite analysis revealed the occurrence of maternal uniparental disomy (UPD) for chromosome 4 in the patient. As a consequence of segmental isodisomy at 4q12, the patient inherited two identical SGCB alleles carrying a missense mutation predicted to result in abnormal protein function. SNP array technology proved to be an elegant means to determine the most probable mechanism of UPD formation in this case, and enabled us to determine the location of recombination events along chromosome 4. In our patient, UPD likely arose from a trisomy rescue event due to maternal meiotic non-disjunction that we speculate may have been caused by abnormal recombination at the pericentromeric region. Maternal UPD 4 is a rare finding, and to our knowledge this is the first reported case of UPD in association with LGMD.

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