Deficiency of the 50 kDa dystrophin-associated-glycoprotein (adhalin) in an Indian autosomal recessive limb girdle muscular dystrophy patient : immunochemical analysis and clinical aspects.
Abnormalities of dystrophin are a common cause of muscular dystrophy and testing for dystrophin gene or protein has become a part of routine diagnostic evaluation of patients who present with progressive proximal muscle weakness, high serum creatine kinase concentrations, and histopathological evidence of a dystrophic process. Patients who have no dystrophin abnormalities are assumed to have autosomal recessive muscular dystrophy. In a family consisting of 5 sibs, 2 mentally normal brothers presented with abnormal gait and protrusion of chest and hips. Muscle biopsy from one of them showed dystrophic changes and reduced patchy binding of dystrophin. No detectable deletion was observed in the patient's DNA and his brother with cDMD probes. Dystrophin associated proteins, beta-dystroglycan showed discontinuous immunostaining in the sarcolemma and alpha-sarcoglycan (adhalin) was totally absent, while beta-, gamma-, and delta-sarcoglycans were highly reduced. Immunoblot analysis showed dystrophin of normal molecular weight but of decreased quantity, beta-dystroglycan was reduced by about 37% while alpha-sarcoglycan was completely absent. This study is a first attempt for a systematic clinical, genetic and molecular investigation of the autosomal recessive LGMD in India.
Handa
V
V
Human Molecular Genetics Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Mital
A
A
Gupta
M
M
Goyle
S
S
D000293:Adolescent; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000172:deficiency / Q000235:genetics*; D049030:Dystroglycans; D016189:Dystrophin / Q000032:analysis / Q000172:deficiency / Q000235:genetics; D005808:Genes, Recessive; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000172:deficiency / Q000235:genetics*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology; D049031:Sarcoglycans
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D016189:Dystrophin; D008562:Membrane Glycoproteins; D049031:Sarcoglycans; D049030:Dystroglycans