Author(s): V. Allamand;Y. Sunada;M. A. Salih;V. Straub;C. O. Ozo;M. H. Al-Turaiki;M. Akbar;T. Kolo;H. Colognato;X. Zhang;L. M. Sorokin;P. D. Yurchenco;K. Tryggvason;K. P. Campbell
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.
Keywords: Amino Acid Sequence Base Sequence Binding Sites Child, Preschool Consanguinity Conserved Sequence Female Fluorescent Antibody Technique Humans Immunoblotting Infant Laminin/ genetics/immunology/metabolism Male Molecular Sequence Data Muscle, Skeletal/immunology Muscular Dystrophies/ congenital/ genetics Polymerase Chain Reaction Pregnancy RNA Splicing Saudi Arabia Sequence Deletion