Beta-sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex.
The dystrophin associated proteins (DAPs) are good candidates for harboring primary mutations in the genetically heterogeneous autosomal recessive muscular dystrophies (ARMD). The transmembrane components of the DAPs can be separated into the dystroglycan and the sarcoglycan complexes. Here we report the isolation of cDNAs encoding the 43 kD sarcoglycan protein beta-sarcoglycan (A3b) and the localization of the human gene to chromosome 4q12. We describe a young girl with ARMD with truncating mutations on both alleles. Immunostaining of her muscle biopsy shows specific loss of the components of the sarcoglycan complex (beta-sarcoglycan, alpha-sarcoglycan (adhalin), and 35 kD sarcoglycan). Thus secondary destabilization of the sarcoglycan complex may be an important pathophysiological event in ARMD.
Bönnemann
C G
CG
Howard Hughes Medical Institute/Division of Genetics, Children's Hospital, Boston, Massachusetts 02115, USA.
Modi
R
R
Noguchi
S
S
Mizuno
Y
Y
Yoshida
M
M
Gussoni
E
E
McNally
E M
EM
Duggan
D J
DJ
Angelini
C
C
Hoffman
E P
EP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics*; D018076:DNA, Complementary / Q000302:isolation & purification; D049030:Dystroglycans; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009132:Muscles / Q000737:chemistry; D009136:Muscular Dystrophies / Q000235:genetics*; D009154:Mutation; D012333:RNA, Messenger / Q000737:chemistry; D011817:Rabbits; D014018:Tissue Distribution
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D049030:Dystroglycans