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Severe γ-sarcoglycanopathy caused by a novel missense mutation and a large deletion
Journal article   Peer reviewed

Severe γ-sarcoglycanopathy caused by a novel missense mutation and a large deletion

K.J. Nowak, P. Walsh, R.L. Jacob, R.D. Johnsen, J. Peverall, E.M. McNally, S.D. Wilton, B.A. Kakulas and N.G. Laing
Neuromuscular Disorders, Vol.10(2), pp.100-107
2000
DOI: https://doi.org/10.1016/S0960-8966(99)00063-2
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Abstract

We report two siblings with a relatively severe limb-girdle muscular dystrophy. The elder sister presented at 8 years of age with inability to climb and abnormal gait. At 12 years she was barely ambulant. Her sister followed a similar course. Serum creatine kinase was 8500–10 000 IU (N 25–200) in the elder sister and 17 000–19 000 IU in the younger sister. Muscle biopsy of the elder sister at 8 years showed chronic myopathic changes with loss of muscle fibres, active necrosis and regeneration. Immunocytochemistry demonstrated normal spectrin and dystrophin, reduced α-sarcoglycan and absent γ-sarcoglycan – indicating a γ-sarcoglycanopathy. Haplotype analysis for the markers D13S115, D13S232, D13S292, D13S787, D13S1243 and D13S283 internal to and flanking the γ-sarcoglycan gene showed the affected sisters shared haplotypes, indicating it was possible they were suffering from a γ-sarcoglycanopathy. Non-inheritance of paternal alleles for D13S232, D13S292 and D13S1243 suggested the inheritance of a deletion, which was confirmed by FISH, using a genomic probe from the γ-sarcoglycan gene. The γ-sarcoglycan cDNA was amplified by reverse transcriptase PCR from the muscle biopsy of the elder sister and sequenced. A missense mutation changing codon 69 from GGC glycine to CGC arginine was identified. HhaI digestion of exon 3 genomic PCR products showed the two affected sisters were hemizygous for the mutation, while the mother and grandmother were heterozygotes. The mutation, identified by SSCP analysis, was not observed in 116 unrelated, unaffected individuals. Previously, only two other missense mutations, the Cys283Tyr missense mutation in Gypsies and the Leu193Ser mutation in a Dutch family, have been described in the γ-sarcoglycan gene. The fact that the affected individuals in the current and Gypsy families are γ-sarcoglycan negative may indicate that codons 69 and 283 are important in γ-sarcoglycan function.

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Collaboration types
Domestic collaboration
International collaboration
Citation topics
1 Clinical & Life Sciences
1.255 Musculoskeletal Disorders
1.255.628 Duchenne Muscular Dystrophy
Web Of Science research areas
Clinical Neurology
Neurosciences
ESI research areas
Neuroscience & Behavior
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