SSCP detection of β-sarcoglycan mutations in limb girdle muscular dystrophy patients

Mutations in α-, β-, γ- and δ-sarcoglycan genes are responsible for four limb-girdle muscular dystrophies. We evaluated by immunohistochemistry α-, β-, γand δ-sarcoglycans in 24 patients and found variable expression of these proteins. In patients with major reduction or exclusive absence of β or γ-sarcoglycan, PCR products, amplified from cDNA by using three overlapping primer pairs, were analysed by SSCP. Altered γ-sarcoglycan conformers were found in 7 patients, altered β-sarcoglycan conformers were found in 2 patients. In one patient with altered β-sarcoglycan conformers all three β-sarcoglican segments were abnormal suggesting a compound heterozygous condition. Sequence analysis showed a duplication in the overlapping region of the first two segments. This mutation previously described in three other Italian patients (Duggan et al. 1997) cause a frame shift and a stop codon at position 129. Our patient is a 26 yearold male presenfcg high CK levels, moderate muscle weakness and slow disease progression. A paternal female cousin showed progressive limb muscle weakness since ealrly childhood and was confined to a wheelchair at age 15. Her parents were first cousins. SSCP analysis of the patient's father and of the paternal uncle, both asymptomatic, showed the same alteration in βl and β2 conformers. The second mutation in our patient is now being investigated.