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Whole exome sequencing identifies a novel mutation in the transglutaminase 6 gene for spinocerebellar ataxia in a Chinese family

Authors

  • M Li,

    1. Department of Psychiatry
    2. Centre for Reproduction, Development and Growth
    3. Centre for Genomic Sciences
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    • These authors contributed equally to this work.

  • SYY Pang,

    1. Department of Medicine
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    • These authors contributed equally to this work.

  • Y Song,

    1. Department of Biochemistry, University of Hong Kong, Hong Kong, China
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  • MHW Kung,

    1. Department of Medicine
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  • S-L Ho,

    Corresponding author
    1. Department of Medicine
    • Pak-Chung Sham, Department of Psychiatry, Room 6-05A, The Hong Kong Jockey Club Building for Interdisciplinary Research, University of Hong Kong,
      5 Sassoon Road, Pokfulam,
      Hong Kong, China.
      Tel.: +852 28315425;
      fax: +852 28185653;
      e-mail: pcsham@hku.hk

      Shu-Leong Ho, Division of Neurology, Department of Medicine, University of Hong Kong, Hong Kong, China.
      Tel.: +852 22553315;
      fax: +852 29741171;
      e-mail: slho@hku.hk

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  • P-C Sham

    Corresponding author
    1. Department of Psychiatry
    2. Centre for Reproduction, Development and Growth
    3. Centre for Genomic Sciences
    • Pak-Chung Sham, Department of Psychiatry, Room 6-05A, The Hong Kong Jockey Club Building for Interdisciplinary Research, University of Hong Kong,
      5 Sassoon Road, Pokfulam,
      Hong Kong, China.
      Tel.: +852 28315425;
      fax: +852 28185653;
      e-mail: pcsham@hku.hk

      Shu-Leong Ho, Division of Neurology, Department of Medicine, University of Hong Kong, Hong Kong, China.
      Tel.: +852 22553315;
      fax: +852 29741171;
      e-mail: slho@hku.hk

    Search for more papers by this author

Abstract

Li M, Pang SYY, Song Y, Kung MHW, Ho S-L, Sham P-C. Whole exome sequencing identifies a novel mutation in the transglutaminase 6 gene for spinocerebellar ataxia in a Chinese family.

Autosomal dominant spinocerebellar ataxias (SCA) constitute a heterogeneous group of inherited disorders. The transglutaminase 6 (TGM6) gene was recently suggested as a SCA causative gene in Chinese SCA families. In this study, two affected members of a three-generation Chinese family with SCA characterized by progressive cerebellar ataxia and lower limb pyramidal signs were subjected to whole exome sequencing. Through bioinformatics analysis of the sequence variants in these two individuals, we identified a novel mutation in the TGM6 gene (c.1528G>C) which showed perfect co-segregation with disease phenotype in all nine members of this family. This finding confirms that mutations in TGM6 gene represent an important cause of SCA in Chinese. This study also shows that whole exome sequencing of a small number of affected individuals, leveraged on bioinformatics analysis, can be an efficient strategy for identifying causative mutations in rare Mendelian disorders.

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