Mild congenital muscular dystrophy in two patients with an internally deleted laminin alpha 2-chain

Congenital muscular dystrophy (CMD) is a group of clinically and genetically heterogeneous disorders inherited in an autosomal recessive mode, The alpha 2-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 alpha 2-chain has recently been reported with the identification of mutations in the gene encoding the alpha 2-chain of laminin 2 (LAMA2) in CMD patients, Here we report on two siblings from a consanguineous family expressing an internally deleted laminin alpha 2-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 alpha 2-chain, Interestingly, these patients appear mildly affected compared to others who completely lack this protein. This situation presents a striking analogy with Decker 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.