title: Primary adhalin deficiency as a cause of muscular dystrophy in patients with normal dystrophin.
abstract: In our experience, more than half of muscular dystrophy patients show a primary dystrophinopathy. The underlying cause of muscular dystrophy in the vast majority of patients with normal dystrophin is unknown. Recently, a French family with 4 young siblings showing a muscular dystrophy of unknown progression was shown to have a primary deficiency of "adhalin," the 50-kd dystrophin-associated protein. Here we report the screening of the entire adhalin coding sequence in muscle biopsy specimens from 30 muscular dystrophy patients to (1) determine whether adhalin deficiency is restricted to the French population, (2) determine the incidence of adhalin deficiency in muscular dystrophy patients, and (3) characterize the clinical features and mutations in adhalin-deficient patients. We identified a single African-American girl with childhood-onset muscular dystrophy and adhalin gene mutations. We found her to be a compound heterozygote for two different mutations of the same amino acid (Arg98Cys; Arg98His), one of which was previously identified in the French family. Our results suggest that primary adhalin deficiency in patients with muscular dystrophy but normal dystrophin is relatively infrequent, and that adhalin-deficient patients are not restricted to the French population.
authors.affiliation: Department of Molecular Genetics, University of Pittsburgh School of Medicine, PA 15261, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ljunggren
authors.forename: D
authors.initials: D
authors.lastname: Duggan
authors.forename: E
authors.initials: E
authors.lastname: McNally
authors.forename: K B
authors.initials: KB
authors.lastname: Boylan
authors.forename: C H
authors.initials: CH
authors.lastname: Gama
authors.forename: L M
authors.initials: LM
authors.lastname: Kunkel
authors.forename: E P
authors.initials: EP
authors.lastname: Hoffman
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics; D016189:Dystrophin / Q000032:analysis*; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D008969:Molecular Sequence Data; D009132:Muscles / Q000737:chemistry* / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D012016:Reference Values; D049031:Sarcoglycans
chemical_list: D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008562:Membrane Glycoproteins; D049031:Sarcoglycans