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Identification of a Novel Mutation in the Titin Gene in a Chinese Family with Limb-Girdle Muscular Dystrophy 2J

Molecular Neurobiology volume 53, pages 5097–5102 (2016)Cite this article

Abstract

Limb-girdle muscular dystrophies (LGMD) are a highly heterogeneous group of genetic myopathies characterized by progressive proximal pelvic and/or shoulder girdle muscle weakness, with the onset ages ranging from early childhood to late adulthood. The identification of these dystrophies through genetic testing will not only inform long-term prognosis but will also assist in directing care more efficiently, including more frequent cardiorespiratory monitoring and prophylactic treatments. The aim of this study was to identify the responsible gene in a five-generation Chinese Han pedigree with autosomal recessive LGMD. Exome sequencing was conducted and a novel mutation c.107788T>C (p.W35930R) in the titin gene (TTN) was identified. The mutation co-segregated with the disorder in the family and was absent in normal controls. Our discovery broadens the mutation spectrum of the TTN gene associated with LGMD2J.

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Fig. 1

Abbreviations

LGMD:

Limb-girdle muscular dystrophies

CK:

Creatine kinase

EMG:

Electromyography

TTN :

The titin gene

ESP:

Exome sequencing project

SIFT:

Sorting intolerant from tolerant

PolyPhen-2:

Polymorphism phenotyping version 2

TMD:

Tibial muscular dystrophy

CNV:

Copy number variation

SNPs:

Single nucleotide polymorphisms

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Acknowledgments

This study was supported by grants 81441033 and 81271921 from the National Natural Science Foundation of China (H.D.), grant 2015JJ4088 from the Natural Science Foundation of Hunan Province, China (W.Z.), grant 2015zzts318 from the Fundamental Research Funds of Central South University, China, grant for the Foster Key Subject of the Third Xiangya Hospital Clinical Laboratory Diagnostics (H.D.), grant for Zhishan Lead Project of the Third Xiangya Hospital (H.D.), and grant for Hunan Provincial Innovation Foundation for Postgraduate, China (7138000008).

Conflict of Interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China

    Wen Zheng, Han Chen, Yan Yang, Zhi Song & Hao Deng

  2. Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Changsha, China

    Wen Zheng, Xiong Deng, Lamei Yuan, Zhijian Yang, Yuan Wu & Hao Deng

  3. Department of Clinical Laboratory, The Third Xiangya Hospital, Central South University, Changsha, China

    Yuan Wu

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  1. Wen Zheng
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  2. Han Chen
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Correspondence to Hao Deng.

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Zheng, W., Chen, H., Deng, X. et al. Identification of a Novel Mutation in the Titin Gene in a Chinese Family with Limb-Girdle Muscular Dystrophy 2J. Mol Neurobiol 53, 5097–5102 (2016). https://doi.org/10.1007/s12035-015-9439-0

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  • DOI: https://doi.org/10.1007/s12035-015-9439-0

Keywords

  • Limb-girdle muscular dystrophies
  • Exome sequencing
  • TTN
  • Mutation
  • Genetic testing