Case reportConserved expression of truncated telethonin in a patient with limb-girdle muscular dystrophy 2G

- We describe a patient with limb-girdle muscular dystrophy and a novel mutation in the TCAP gene.
- The mutation generates a truncated telethonin of predicted molecular mass of ~10 kDa.
- Expression and localization of the mutant protein is retained in this patient's muscle.
- Absence of telethonin labeling is considered a highly specific diagnostic feature for LGMD2G.
- Our data suggest that patients with mutations in TCAP and retention of protein expression may exist.

Limb-girdle muscular dystrophy 2G is caused by mutations in the TCAP gene that encodes for telethonin. Here we describe a 49 year-old male patient of Indian descent presenting a classical LGMD phenotype. He had normal motor milestones but became noticeably slower in his early teens and was wheelchair bound by age 44. The muscle biopsy showed myopathic features and absence of labeling with an antibody to the C-terminal portion of telethonin. Sequence analysis of the TCAP gene revealed a novel homozygous mutation in exon 2, predicted to generate a truncated protein of 81 amino acids. Interestingly, an antibody for the full-length protein showed labeling on sections and a single band of ~10 kDa on Western blot. The truncated protein co-localized with filamin C at the Z-line. Our findings indicate that mutant telethonin can be incorporated into the sarcomere and that other LGMD2G patients with retention of telethonin expression may exist.