title: Abnormalities in alpha-, beta- and gamma-sarcoglycan in patients with limb-girdle muscular dystrophy.
abstract: We have identified 12 cases from a group of 45 patients with early onset limb-girdle muscular dystrophy (LGMD), who have a deficiency of the 50 kDa dystrophin-associated glycoprotein, alpha-sarcoglycan. An additional male sibling of one case was also studied clinically. All 12 patients showed a concomitant, but variable, deficiency of alpha-, beta- and gamma-sarcoglycan. None of our patients had a defect in only one component of the sarcoglycan complex. Molecular analysis confirmed that a total absence of one sarcoglycan, associated with reduced expression of the other two, indicates a primary defect. Immunocytochemistry is thus useful for directing molecular studies. Morphological features not usually observed in Xp21 dystrophies were peripheral accumulations of mitochondria, discrete core-like areas, and nemaline rods in one case. Clinical severity and progression was variable between and within families but early loss of ambulation, at or before the age of 12 years, was associated with a total absence of gamma-sarcoglycan. Common clinical features were calf hypertrophy, contractures of the tendo achilles, lumbar lordosis, winging of the scapulae, weak hamstrings and weak neck muscles. All cases had grossly elevated serum creatine kinase. In contrast to patients with Duchenne muscular dystrophy (DMD), our patients with sarcoglycan deficiencies had normal early motor milestones, normal intellect, and good respiratory and cardiac function. Our data confirm that the sarcoglycan complex acts as a unit and that morphological and clinical features can distinguish patients with defects in the sarcoglycans from those with Xp21 dystrophy. In our group of patients prognosis is better than in DMD, but clinical variability makes this difficult to predict in isolated cases.
authors.affiliation: Department of paediatrics and Neonatal Medicine, MRC Clinical Sciences Centre, Royal postgraduate Medical School, London, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Sewry
authors.forename: J
authors.initials: J
authors.lastname: Taylor
authors.forename: L V
authors.initials: LV
authors.lastname: Anderson
authors.forename: E
authors.initials: E
authors.lastname: Ozawa
authors.forename: R
authors.initials: R
authors.lastname: Pogue
authors.forename: F
authors.initials: F
authors.lastname: Piccolo
authors.forename: K
authors.initials: K
authors.lastname: Bushby
authors.forename: V
authors.initials: V
authors.lastname: Dubowitz
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000172:deficiency*; D018450:Disease Progression; D049030:Dystroglycans; D016189:Dystrophin; D005121:Extremities; D005260:Female; D005808:Genes, Recessive; D006321:Heart / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency*; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology*; D009136:Muscular Dystrophies / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D012129:Respiratory Function Tests; D049031:Sarcoglycans
chemical_list: D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D016189:Dystrophin; D008562:Membrane Glycoproteins; D049031:Sarcoglycans; D049030:Dystroglycans