title: Mutations in the integrin alpha7 gene cause congenital myopathy.
abstract: The basal lamina of muscle fibers plays a crucial role in the development and function of skeletal muscle. An important laminin receptor in muscle is integrin alpha7beta1D. Integrin beta1 is expressed throughout the body, while integrin alpha7 is more muscle-specific. To address the role of integrin alpha7 in human muscle disease, we determined alpha7 protein expression in muscle biopsies from 117 patients with unclassified congenital myopathy and congenital muscular dystrophy by immunocytochemistry. We found three unrelated patients with integrin alpha7 deficiency and normal laminin alpha2 chain expression. To determine if any of these three patients had mutations of the integrin alpha7 gene, ITGA7, we cloned and sequenced the full-length human ITGA7 cDNA, and screened the patients for mutations. One patient had splice mutations on both alleles; one causing a 21-bp insertion in the conserved cysteine-rich region, and the other causing a 98-bp deletion. A second patient was a compound heterozygote for the same 98-bp deletion, and had a 1-bp frame-shift deletion on the other allele. A third showed marked deficiency of ITGA7 mRNA. Clinically, these patients showed congenital myopathy with delayed motor milestones. Our results demonstrate that mutations in ITGA7 are involved in a form of congenital myopathy.
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: Y K
authors.initials: YK
authors.lastname: Hayashi
authors.forename: F L
authors.initials: FL
authors.lastname: Chou
authors.forename: E
authors.initials: E
authors.lastname: Engvall
authors.forename: M
authors.initials: M
authors.lastname: Ogawa
authors.forename: C
authors.initials: C
authors.lastname: Matsuda
authors.forename: S
authors.initials: S
authors.lastname: Hirabayashi
authors.forename: K
authors.initials: K
authors.lastname: Yokochi
authors.forename: B L
authors.initials: BL
authors.lastname: Ziober
authors.forename: R H
authors.initials: RH
authors.lastname: Kramer
authors.forename: S J
authors.initials: SJ
authors.lastname: Kaufman
authors.forename: E
authors.initials: E
authors.lastname: Ozawa
authors.forename: Y
authors.initials: Y
authors.lastname: Goto
authors.forename: I
authors.initials: I
authors.lastname: Nonaka
authors.forename: T
authors.initials: T
authors.lastname: Tsukahara
authors.forename: J Z
authors.initials: JZ
authors.lastname: Wang
authors.forename: E P
authors.initials: EP
authors.lastname: Hoffman
authors.forename: K
authors.initials: K
authors.lastname: Arahata
mesh_terms: D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005260:Female; D006801:Humans; D007223:Infant; D039001:Integrin alpha Chains; D008297:Male; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D009135:Muscular Diseases / Q000151:congenital* / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D015703:Antigens, CD; D018076:DNA, Complementary; D039001:Integrin alpha Chains; D012333:RNA, Messenger; C085725:integrin alpha7