Article

Limb girdle muscular dystrophies are rare genetic diseases. Despite
constant progress in genetics and biochemistry, the pathogenic mechanisms are not
completely understood. Calpainopathy (LGMD2A) has been reported to be the most
frequent autosomal recessive form of muscular dystrophy in several populations.
Point mutations in CAPN3 are difficult to identify and the analysis is long and
costly. The use of western blot does not seem to provide the expected sensitivity
and specificity. METHOD: We studied all the patients diagnosed in
the neuromuscular center of Bordeaux (France) with confirmed calpainopathy in
order to establish the appropriate diagnostic approach (inclusion criteria:
muscular biopsy with calpain 3 western blot study, two mutations in CAPN3).
Patients with highly suspected calpainopathy (same criteria with only one
mutation) were also analyzed. RESULTS: Our 13 patients belonged to 10 different
families. Four patients had a normal western blot for calpain (WBn). We found
high phenotypic variability with frequent atypical signs. The WBn group had less
severe disease (a statistically significant later age of onset, a tendency toward
lower CK levels and a slower disease course). We extended this comparison to the
single mutation patients and we found the same results. CONCLUSION: Considering
the lack of sensitivity of western blot protein analysis in LGMD2A, a normal
western blot for calpain should not halt the genetic analysis. The western blot
result seems to have prognostic value. A normal western blot may help genetic
testing by highlighting some mutational hot spots in the CAPN3 gene.
CI - Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

Langue : FRANCAIS