title: Novel TCAP mutation c.32C>A causing limb girdle muscular dystrophy 2G.
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.
authors: CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
authors: Amirtharaj
authors: A
authors: Francis
authors: Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, India.
authors: Balaraju
authors: B
authors: Sunitha
authors: CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
authors: Kandavalli
authors: K
authors: Vinodh
authors: Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India.
authors: Kiran
authors: K
authors: Polavarapu
authors: CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
authors: Shiva Krishna
authors: SK
authors: Katkam
authors: Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India.
authors: Sailesh
authors: S
authors: Modi
authors: Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bengaluru, India.
authors: M M Srinivas
authors: MM
authors: Bharath
authors: Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, India.
authors: Narayanappa
authors: N
authors: Gayathri
authors: Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India.
authors: Atchayaram
authors: A
authors: Nalini
authors: CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
authors: Kumarasamy
authors: K
authors: Thangaraj
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D064211:Connectin / Q000235:genetics* / Q000378:metabolism; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D015151:Immunoblotting; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010375:Pedigree; D055815:Young Adult
chemical_list: D064211:Connectin; C577292:TCAP protein, human