The effect of calpain 3 deficiency on the pattern of muscle degeneration in the earliest stages of LGMD2A.
Limb girdle muscular dystrophy type 2A (LGMD2A) is caused by mutations in the calpain 3 gene. In a large family affected by LGMD2A with four severely affected members, three additional asymptomatic relatives had very high serum creatine kinase concentrations. All were homozygous for the R110X mutation and showed a total absence of calpain 3 in the muscle. Histological analysis of muscle in these three rare preclinical cases showed a consistent but unusual pattern, with isolated fascicles of degenerating fibres in an almost normal muscle. This pattern was also seen in one patient with early stage LGMD2A who had a P82L missense mutation and a partial deficiency of calpain 3 in the muscle, but was not seen in early stage patients affected by other forms of LGMD. These findings suggest that a peculiar pattern of focal degeneration occurs in calpainopathy, independently of the type of mutation or the amount of calpain 3 in the muscle.
Vainzof
M
M
Human Genome Research Centre, Department of Biology, IBUSP, University of São Paulo, São Paulo, Sao Paulo - CEP, 05508-900, SP Brazil.
de Paula
F
F
Tsanaclis
A M
AM
Zatz
M
M
D002154:Calpain / Q000032:analysis / Q000172:deficiency* / Q000235:genetics; D016022:Case-Control Studies; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000473:pathology*; D009136:Muscular Dystrophies / Q000201:enzymology* / Q000473:pathology*; D009154:Mutation
D007527:Isoenzymes; D009124:Muscle Proteins; C105884:CAPN3 protein, human; D002154:Calpain