Key result
Genetic analysis of Indian patients with LGMD2G identified a novel nonsense homozygous mutation c.32C>A and a homozygous duplication c.26_33dupAGGTGTCG in the TCAP gene, both leading to truncated telethonin protein.
Observational (n=300)
No
This study expands the genetic spectrum of LGMD2G by identifying a novel TCAP mutation in the Indian population and confirms the absence of cardiac involvement in these patients despite TCAP's role in cardiac sarcomeres.
Novel TCAP mutations expand Indian LGMD2G spectrum; supports absent cardiac involvement but leaves generalizability open.
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.
No takes yet. Share an insight, caveat, or question.
Francis et al. (2014) conducted an observational in Limb Girdle Muscular Dystrophy 2G (LGMD2G) (n=300). TCAP gene mutations vs. Unaffected family members and healthy controls was evaluated on Identification of TCAP mutations causing LGMD2G. Genetic analysis of Indian patients with LGMD2G identified a novel nonsense homozygous mutation c.32C>A and a homozygous duplication c.26_33dupAGGTGTCG in the TCAP gene, both leading to truncated telethonin protein.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: