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

PLoS One. 2014 Jul 23;9(7):e102763. doi: 10.1371/journal.pone.0102763. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Child
  • Connectin / genetics*
  • Connectin / metabolism
  • Consanguinity
  • DNA Mutational Analysis
  • Family Health
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Homozygote
  • Humans
  • Immunoblotting
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Muscular Dystrophies, Limb-Girdle / genetics*
  • Muscular Dystrophies, Limb-Girdle / metabolism
  • Mutation*
  • Pedigree
  • Young Adult

Substances

  • Connectin
  • TCAP protein, human

Supplementary concepts

  • Muscular Dystrophy, Limb-Girdle, Type 2G

Grants and funding

This study was funded by Department of Science and Technology (DST) Government of India (F.No. SR/SO/HS-16/2009) and KT was supported by CSIR Network project - GENESIS (BSC0121), Government of India. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.