Beta-sarcoglycan: characterization and role in limb-girdle muscular dystrophy linked to 4q12.
beta-Sarcoglycan, a 43 kDa dystrophin-associated glycoprotein, is an integral component of the dystrophin-glycoprotein complex. We have cloned human beta-sarcoglycan cDNA and mapped the beta-sarcoglycan gene to chromosome 4q12. Pericentromeric markers and an intragenic polymorphic CA repeat cosegregated perfectly with autosomal recessive limb-girdle muscular dystrophy in several Amish families. A Thr-to-Arg missense mutation was identified within the beta-sarcoglycan gene that leads to a dramatically reduced expression of beta-sarcoglycan in the sarcolemma and a concomitant loss of adhalin and 35 DAG, which may represent a disruption of a functional subcomplex within the dystrophin-glycoprotein complex. Thus, the beta-sarcoglycan gene is the fifth locus identified (LGMD2E) that is involved in autosomal recessive limb-girdle muscular dystrophy.
Lim
L E
LE
Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242, USA.
Duclos
F
F
Broux
O
O
Bourg
N
N
Sunada
Y
Y
Allamand
V
V
Meyer
J
J
Richard
I
I
Moomaw
C
C
Slaughter
C
C
D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics*; D018076:DNA, Complementary; D049030:Dystroglycans; D005006:Ethnicity / Q000235:genetics; D006801:Humans; D007196:Indiana; D008562:Membrane Glycoproteins / Q000032:analysis / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics*; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics*; D009154:Mutation; D049031:Sarcoglycans; D012508:Sarcolemma / Q000737:chemistry; D014018:Tissue Distribution
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D049031:Sarcoglycans; D049030:Dystroglycans