Identification of a Novel Mutation in the Titin Gene in a Chinese Family with Limb-Girdle Muscular Dystrophy 2J
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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.
KeywordsLimb-girdle muscular dystrophies Exome sequencing TTN Mutation Genetic testing
Limb-girdle muscular dystrophies
The titin gene
Exome sequencing project
Sorting intolerant from tolerant
Polymorphism phenotyping version 2
Tibial muscular dystrophy
Copy number variation
Single nucleotide polymorphisms
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.
This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
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