Novel TCAP Mutation c.32C>A Causing Limb Girdle Muscular Dystrophy 2G |
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| Authors: | Amirtharaj Francis Balaraju Sunitha Kandavalli Vinodh Kiran Polavarapu Shiva Krishna Katkam Sailesh Modi M M Srinivas Bharath Narayanappa Gayathri Atchayaram Nalini Kumarasamy Thangaraj |
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| Institution: | 1. CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.; 2. Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, India.; 3. Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India.; 4. Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bengaluru, India.; Stem Cell Research Institute, Belgium, |
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| Abstract: | TCAP encoded telethonin is a 19 kDa protein, which plays an important role in anchoring titin in Z disc of the sarcomere, and is known to cause LGMD2G, a rare muscle disorder characterised by proximal and distal lower limb weakness, calf hypertrophy and loss of ambulation. A total of 300 individuals with ARLGMD were recruited for this study. Among these we identified 8 clinically well characterised LGMD2G cases from 7 unrelated Dravidian families. Clinical examination revealed predominantly proximo - distal form of weakness, scapular winging, muscle atrophy, calf hypertrophy and foot drop, immunoblot showed either complete absence or severe reduction of telethonin. Genetic analysis revealed a novel nonsense homozygous mutation c.32C>A, p.(Ser11*) in three patients of a consanguineous family and an 8 bp homozygous duplication c.26_33dupAGGTGTCG, p.(Arg12fs31*) in another patient. Both mutations possibly lead to truncated protein or nonsense mediated decay. We could not find any functionally significant TCAP mutation in the remaining 6 samples, except for two other polymorphisms, c.453A>C, p.( = ) and c.-178G>T, which were found in cases and controls. This is the first report from India to demonstrate TCAP association with LGMD2G. |
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