Novel TCAP mutation c.32C>A causing limb girdle muscular dystrophy 2G

Francis, Amirtharaj ; Sunitha, Balaraju ; Vinodh, Kandavalli ; Polavarapu, Kiran ; Katkam, Shiva Krishna ; Modi, Sailesh ; Bharath, M. M. Srinivas ; Gayathri, Narayanappa ; Nalini, Atchayaram ; Thangaraj, Kumarasamy (2014) Novel TCAP mutation c.32C>A causing limb girdle muscular dystrophy 2G PLoS One, 9 (7). Article ID e102763-11 pages. ISSN 1932-6203

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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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