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

Am J Med Genet. 1999 Feb 19;82(5):392-8. doi: 10.1002/(sici)1096-8628(19990219)82:5<392::aid-ajmg7>3.0.co;2-0.

Abstract

The autosomal recessive limb-girdle muscular dystrophies (AR-LGMDs) are a heterogeneous group of disorders of progressive weakness of the pelvic and shoulder girdle musculature. The clinical course is characterized by great variability, ranging from severe forms with onset in the first decade and rapid progression resembling clinically Xp21 Duchenne muscular dystrophy (DMD) to milder forms with later onset and slower course. Eight genes are mapped 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 (6-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 families. Linkage analysis in two unlinked families excluded the eight AR-LGMD genes, indicating that there is at least one more gene responsible for AR-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 condition, but considerable inter- and intra-familial clinical variability was observed among patients from all other groups; 2) serum CK activities showed the highest values in LGMD2D (alpha-SG) patients among sarcoglycanopathies and LGMD2B (dysferlin) patients among nonsarcoglycanopathies; 3) comparison between LGMD2A (CAPN3) and LGMD2B (dysferlin) showed that the first have 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 approximately 70% of LGMD2B patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Brazil
  • Calpain / genetics
  • Child
  • Child, Preschool
  • Connectin
  • Creatine Kinase / blood
  • Cytoskeletal Proteins / genetics
  • Dysferlin
  • Dystroglycans
  • Female
  • Genotype
  • Humans
  • Isoenzymes*
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Proteins*
  • Middle Aged
  • Muscle Proteins / genetics
  • Muscular Dystrophies / classification
  • Muscular Dystrophies / ethnology
  • Muscular Dystrophies / genetics*
  • Mutation
  • Mutation, Missense
  • Peptide Fragments / genetics
  • Phenotype
  • Sarcoglycans

Substances

  • Connectin
  • Cytoskeletal Proteins
  • DAG1 protein, human
  • DYSF protein, human
  • Dysferlin
  • Isoenzymes
  • Membrane Glycoproteins
  • Membrane Proteins
  • Muscle Proteins
  • Peptide Fragments
  • Sarcoglycans
  • TCAP protein, human
  • Dystroglycans
  • Creatine Kinase
  • CAPN3 protein, human
  • Calpain
  • Capn3 protein, mouse