title: 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.
authors.affiliation: Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: F
authors.initials: F
authors.lastname: Duclos
authors.forename: O
authors.initials: O
authors.lastname: Broux
authors.forename: N
authors.initials: N
authors.lastname: Bourg
authors.forename: V
authors.initials: V
authors.lastname: Straub
authors.forename: G L
authors.initials: GL
authors.lastname: Feldman
authors.forename: Y
authors.initials: Y
authors.lastname: Sunada
authors.forename: L E
authors.initials: LE
authors.lastname: Lim
authors.forename: F
authors.initials: F
authors.lastname: Piccolo
authors.forename: S
authors.initials: S
authors.lastname: Cutshall
authors.forename: F
authors.initials: F
authors.lastname: Gary
authors.forename: F
authors.initials: F
authors.lastname: Quetier
authors.forename: J C
authors.initials: JC
authors.lastname: Kaplan
authors.forename: C E
authors.initials: CE
authors.lastname: Jackson
authors.forename: J S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: K P
authors.initials: KP
authors.lastname: Campbell
mesh_terms: D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing; D001483:Base Sequence; D002648:Child; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D003598:Cytoskeletal Proteins / Q000235:genetics*; D049030:Dystroglycans; D016189:Dystrophin; D005006:Ethnicity / Q000235:genetics*; D005091:Exons; D005260:Female; D005808:Genes, Recessive; D006580:Genetic Carrier Screening; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D006984:Hypertrophy; D007196:Indiana; D007438:Introns; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009679:Nuclear Family; D017354:Point Mutation
chemical_list: D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D016189:Dystrophin; D008562:Membrane Glycoproteins; D049030:Dystroglycans