Publication:

Beta-sarcoglycan: genomic analysis and identification of a novel missense mutation in the LGMD2E Amish isolate (1998)

Author(s): F. Duclos;O. Broux;N. Bourg;V. Straub;G. L. Feldman;Y. Sunada;L. E. Lim;F. Piccolo;S. Cutshall;F. Gary;F. Quetier;J. C. Kaplan;C. E. Jackson;J. S. Beckmann;K. P. Campbell

  • : Beta-sarcoglycan: genomic analysis and identification of a novel missense mutation in the LGMD2E Amish isolate

Abstract: The sarcoglycan complex is involved in the etiology of four autosomal recessive limb-girdle muscular dystrophies (LGMD2C-F). A missense mutation (T151R) in the beta-sarcoglycan gene on chromosome 4q12 has been shown to cause a mild form of LGMD2E in 11 families from a Southern Indiana Amish community sharing a common haplotype. We now report that two sibs from another Amish family with mild LGMD2E are compound heterozygotes for chromosome 4q12 markers. In order to characterize the genetic defect in this new family, we determined the genomic organization of the beta-sarcoglycan gene. A second missense mutation (R91C) has now been identified in this LGMD2E Amish family. This mutation is also present in the homozygous state in another family of probable Amish ancestry. Finally, analysis of all the components of the dystrophin-glycoprotein complex was performed for the first time on a biopsy from a patient homozygous for the beta-sarcoglycan mutation (T151R). Interestingly, in addition to the loss of the entire sarcoglycan complex, we detected a reduction of alpha-dystroglycan which suggests a role for the sarcoglycan complex in stabilizing alpha-dystroglycan at the sarcolemma.

  • Short Title: Beta-sarcoglycan: genomic analysis and identification of a novel missense mutation in the LGMD2E Amish isolate
  • Date: Feb
  • Journal: Neuromuscul Disord
  • Volume: 8
  • Issue: 1
  • Pages: 30-8
  • Publication type: Article
  • Bibliographic status: Published

Keywords: Adolescent Adult Alternative Splicing Base Sequence Child Chromosome Mapping Chromosomes, Human, Pair 4 Cytoskeletal Proteins/ genetics Dystroglycans Dystrophin Ethnic Groups/ genetics Exons Female Genes, Recessive Haplotypes Heterozygote Detection Homozygote Humans Hypertrophy Indiana Introns Male Membrane Glycoproteins/ genetics Middle Aged Muscle, Skeletal/pathology Muscular Dystrophies/ genetics/pathology/physiopathology Nuclear Family Point Mutation

Staff

Professor Volker Straub
Harold Macmillan Professor of Medicine