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

Area of Science:

• Genetics
• Molecular Biology
• Neurology

Background:

• Telethonin (TCAP) is crucial for sarcomere structure, anchoring titin in the Z-disc.
• Mutations in TCAP cause Limb-Girdle Muscular Dystrophy type 2G (LGMD2G), a rare muscle disorder.
• LGMD2G is characterized by progressive muscle weakness, calf hypertrophy, and ambulation loss.

Purpose of the Study:

• To investigate the genetic basis of LGMD2G in Indian Dravidian families.
• To identify novel mutations in the TCAP gene associated with LGMD2G.
• To characterize the clinical presentation of LGMD2G in the studied cohort.

Main Methods:

• Recruitment of 300 individuals with autosomal recessive LGMD (ARLMD).
• Clinical examination and immunoblotting to assess muscle pathology and telethonin levels.
• Genetic analysis including sequencing to identify mutations in the TCAP gene.

Main Results:

• Identified 8 LGMD2G cases from 7 unrelated Dravidian families.
• Discovered two novel homozygous TCAP mutations: a nonsense mutation (c.32C>A, p.(Ser11*)) and a duplication (c.26_33dupAGGTGTCG, p.(Arg12fs31*)).
• Observed complete absence or severe reduction of telethonin in affected individuals.

Conclusions:

• TCAP gene mutations are a cause of LGMD2G in the Indian population.
• The identified mutations likely lead to truncated proteins or nonsense-mediated decay, causing muscle dysfunction.
• This is the first report linking TCAP mutations to LGMD2G in India.