Seven autosomal recessive limb-girdle muscular dystrophies in the Brazilian population: From LGMD2A to LGMD2G

The autosomal recessive limb-girdle muscular dystrophies (AR-LGMDs) are a h eterogeneous group of disorders of progressive weakness of the pelvic and s houlder girdle musculature. The clinical course is characterized by great v ariability, ranging from severe forms with onset in the first decade and ra pid progression resembling clinically Xp21 Duchenne muscular dystrophy (DMD ) to milder forms with later onset and slower course. Eight genes are mappe d for the AR-LGMDs; they are: LGMD2A (CAPN3) at 15q, LGMD2B (dysferlin) at 2p, LGMD2C (gamma-SG) at 13q, LGMD2D (alpha-SG) at 17q, LGMD2E (beta-SG) at 4q, LGMD2F (delta-SG) at 5q, LGMD2G at 17q, and more recently LGMD2H at 9q . The LGMD2F (delta-SG) and LGMD2G genes were mapped in Brazilian AR-LGMD f amilies. Linkage analysis in two unlinked families excluded the eight AR-LG MD genes, indicating that there is at least one more gene responsible for A R-LGMD. We have analyzed 140 patients (from 40 families) affected with one of seven autosomal recessive LGMD loci, that is, from LGMD2A to LGMD2G. The main observations were: 1) all LGMD2E and LGMD2F patients had a severe con dition, but considerable inter- and intra-familial clinical variability was observed among patients from all other groups; 2) serum CK activities show ed the highest values in LGMD2D (alpha-SG) patients among sarcoglycanopathi es and LGMD2B (dysferlin) patients among nonsarcoglycanopathies; 3) compari son between LGMD2A (CAPN3) and LGMD2B (dysferlin) showed that the first hav e on average a more severe course and have calf hypertrophy more frequently (86% versus 13%); and 4) inability to walk on toes was observed in approxi mately 70% of LGMD2B patients. (C) 1999 Wiley-Liss, Inc.