Conserved expression of truncated telethonin in a patient with limb-girdle muscular dystrophy 2G.
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.
Rare Diseases Advisory Group Service for Neuromuscular Diseases, Muscle Immunoanalysis Unit, Dental Hospital, Richardson Road, Newcastle upon Tyne, UK; The JW Muscular Dystrophy Research Centre and MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. Electronic address: rita.barresi@ncl.ac.uk.
Rita
R
Barresi
Rare Diseases Advisory Group Service for Neuromuscular Diseases, Muscle Immunoanalysis Unit, Dental Hospital, Richardson Road, Newcastle upon Tyne, UK.
Charlotte
C
Morris
The JW Muscular Dystrophy Research Centre and MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Judith
J
Hudson
Department of Cellular Pathology, University Hospital of Birmingham NHS Foundation Trust, Birmingham, UK.
Elizabeth
E
Curtis
The JW Muscular Dystrophy Research Centre and MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Clare
C
Pickthall
The JW Muscular Dystrophy Research Centre and MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Kate
K
Bushby
Department of Neurology, University Hospital of Birmingham NHS Foundation Trust, Birmingham, UK.
Nicholas P
NP
Davies
The JW Muscular Dystrophy Research Centre and MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Volker
V
Straub
D064211:Connectin / Q000235:genetics* / Q000378:metabolism; D057645:Deltoid Muscle / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D012518:Sarcomeres / Q000378:metabolism / Q000473:pathology
D064211:Connectin; C577292:TCAP protein, human
Immunohistochemistry; Limb-girdle muscular dystrophy; Telethonin; Western blot