Noval mutation (Y184C) in exon 4 of the beta-sarcoglycan gene identified in a Portuguese patient. Mutations in brief no. 177. Online.
We report a novel beta-sarcoglycan gene mutation identified in a 21-year-old Portuguese male with a progressive myopathy of intermediate severity, who had been misdiagnosed as Becker Muscular Dystrophy (BMD) based on clinical observations and muscle immunocytochemical anaylsis with dystrophin antibodies only. Since no detectable deletions or duplications were found in the dystrophin gene, we screened for mutations in the sarcoglycan genes by PCR-SSCP. The patient's sample showed a band of increased mobility in exon 4 of the beta-sarcoglycan gene which, upon sequencing, was found to represent a homozygous A-->G transversion at nucleotide 551, resulting in a tyrosine to cysteine substitution at position 184 (Y184C). Carrier status was ascertained in both parents and a sister. These aberrant conformers were not detected in 85 unrelated control individuals screened by PCR-SSCP analysis. All seven beta-sarcoglycan mutations reported to date are associated with a severe phenotype and occur in exons 3 and 4, which correspond to the immediate extracellular domain of the protein. This region contains five conserved cysteine residues. In our patient, the presence of an extra cysteine residue could interefere with intra- and/or inter-molecular disulphide bond formation. The intermediate phenotype could perhaps result from the assembly of both normal and abnormal complexes, depending on the formation of the disulphide bonds.
dos Santos
M R
MR
Unidade de Genética Molecular, Instituto de Genética Médica Jacinto de Magalhães, Porto, Portugal. molecular@igmjm.pt
Jorge
P
P
Ribeiro
E M
EM
Pires
M M
MM
Guimarães
A
A
D000328:Adult; D003598:Cytoskeletal Proteins / Q000235:genetics*; D003937:Diagnosis, Differential; D049030:Dystroglycans; D005091:Exons / Q000235:genetics*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics*
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D049030:Dystroglycans