title: Mild congenital muscular dystrophy in two patients with an internally deleted laminin alpha2-chain.
abstract: Congenital muscular dystrophy (CMD) is a group of clinically and genetically heterogeneous disorders inherited in an autosomal recessive mode. The alpha2-chain of laminin-2 (previously called merosin) has been shown by immunohistochemical and genetic analyses to be implicated in the pathogenesis of the 'classic' form of CMD. In the 'merosin-deficient' subgroup, which represents about half of the cases, more definite evidence of the involvement of the laminin alpha2-chain has recently been reported with the identification of mutations in the gene encoding the alpha2-chain of laminin 2 (LAMA2) in CMD patients. Here we report on two siblings from a consanguineous family expressing an internally deleted laminin alpha2-chain as a result of a splice site mutation in the LAMA2 gene which causes the splicing of exon 25. The predicted protein lacks 63 amino acids in domain IVa which forms a globular structure on the short arm of the alpha2-chain. Interestingly, these patients appear mildly affected compared to others who completely lack this protein. This situation presents a striking analogy with Becker muscular dystrophy, where in-frame deletions in the dystrophin gene result in the expression of a semi-functional protein and lead to a mild phenotype.
authors.affiliation: Howard Hughes Medical Institute and Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: V
authors.initials: V
authors.lastname: Allamand
authors.forename: Y
authors.initials: Y
authors.lastname: Sunada
authors.forename: M A
authors.initials: MA
authors.lastname: Salih
authors.forename: V
authors.initials: V
authors.lastname: Straub
authors.forename: C O
authors.initials: CO
authors.lastname: Ozo
authors.forename: M H
authors.initials: MH
authors.lastname: Al-Turaiki
authors.forename: M
authors.initials: M
authors.lastname: Akbar
authors.forename: T
authors.initials: T
authors.lastname: Kolo
authors.forename: H
authors.initials: H
authors.lastname: Colognato
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: L M
authors.initials: LM
authors.lastname: Sorokin
authors.forename: P D
authors.initials: PD
authors.lastname: Yurchenco
authors.forename: K
authors.initials: K
authors.lastname: Tryggvason
authors.forename: K P
authors.initials: KP
authors.lastname: Campbell
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002675:Child, Preschool; D003241:Consanguinity; D017124:Conserved Sequence; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D007223:Infant; D007797:Laminin / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000276:immunology; D009136:Muscular Dystrophies / Q000151:congenital* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012326:RNA Splicing; D012529:Saudi Arabia; D017384:Sequence Deletion
chemical_list: D007797:Laminin; C102645:laminin alpha 2