Abstract
Congenital muscular dystrophies (CMDs), are heterogeneous autosomal recessive disorders. Their severe manifestations consist of early hypotonia and weakness, markedly delayed motor milestones and contractures, often associated with joint deformities1. Histological changes seen in muscle biopsies consist of large variations in muscle fibre size, a few necrotic and regenerating fibres and a marked increase in endomysial collagen tissue. Diagnosis is based on clinical features and on morphological changes. In several CMD cases, we have demonstrated an absence of one of the components of the extracellular matrix around muscle fibres, the merosin M chain2, now referred to as the α2 chain of laminin-2 (ref. 3). We localized this CMD locus to chromosome 6q2 by homozygosity mapping and linkage analysis4. The laminin α2 chain gene (LAMA2) maps to the same region on chromosome 6q22-23 (ref. 5). We therefore investigated LAMA2 for the presence of disease-causing mutations in laminin α2 chain-deficient CMD families and now report splice site and nonsense mutations in two families leading presumably to a truncated laminin α2 protein.
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Helbling-Leclerc, A., Zhang, X., Topaloglu, H. et al. Mutations in the laminin α2–chain gene (LAMA2) cause merosin–deficient congenital muscular dystrophy. Nat Genet 11, 216–218 (1995). https://doi.org/10.1038/ng1095-216
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DOI: https://doi.org/10.1038/ng1095-216
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