title: Adhalin gene mutations in patients with autosomal recessive childhood onset muscular dystrophy with adhalin deficiency.
abstract: Homozygous adhalin gene mutations were found in three patients from two consanguineous families with autosomal recessive childhood onset muscular dystrophy. Muscle biopsies from patients in each family showed complete absence of adhalin. Sequencing of adhalin cDNA prepared from skeletal muscle by reverse transcription PCR demonstrated a cytosine to thymidine substitution at nt 229 in the patient in family 1 and an adenine to guanine substitution at nt 410 and a 15-base insertion between nt 408 and 409 in the two patients in family 2. Sequencing of genomic DNA prepared from peripheral blood leukocytes by PCR confirmed these mutations. The parents in each family were found to be heterozygous for the respective mutations. These adhalin gene mutations are presumed to be responsible for the absence of adhalin in the skeletal muscle. Adhalin deficiency likely causes disruption of the muscle cell membrane, resulting in dystrophic changes in the skeletal muscle similar to dystrophin deficiency in Duchenne muscular dystrophy.
authors.affiliation: First Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kawai
authors.forename: M
authors.initials: M
authors.lastname: Akaike
authors.forename: T
authors.initials: T
authors.lastname: Endo
authors.forename: K
authors.initials: K
authors.lastname: Adachi
authors.forename: T
authors.initials: T
authors.lastname: Inui
authors.forename: T
authors.initials: T
authors.lastname: Mitsui
authors.forename: S
authors.initials: S
authors.lastname: Kashiwagi
authors.forename: T
authors.initials: T
authors.lastname: Fujiwara
authors.forename: S
authors.initials: S
authors.lastname: Okuno
authors.forename: S
authors.initials: S
authors.lastname: Shin
mesh_terms: D000328:Adult; D017668:Age of Onset; D000595:Amino Acid Sequence; D001483:Base Sequence; D001706:Biopsy; D002648:Child; D003241:Consanguinity; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics*; D017931:DNA Primers; D004251:DNA Transposable Elements; D018076:DNA, Complementary; D005260:Female; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D049031:Sarcoglycans
chemical_list: D003598:Cytoskeletal Proteins; D017931:DNA Primers; D004251:DNA Transposable Elements; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D049031:Sarcoglycans