Primary deficiency of laminin alpha-2 due to mutations in the LAMA2 gene accounts for 30% of all patients with congenital muscular dystrophy. Here, we present seven patients with partial or total laminin alpha-2 deficiency (MDC1A) with a wide clinical spectrum, ranging from ambulant patients to patients who were never able to stand or sit. We identified two pathogenic mutations in the LAMA2 gene in all patients except for one patient in whom only one mutation was found. Six of the mutations were previously undescribed. In some of the milder cases, laminin alpha-2 expression in the muscle biopsy was only slightly reduced. These findings emphasize that analysis of the LAMA2 gene might be necessary in patients with muscle weakness, cerebral white matter changes and high creatine kinase levels, even in the presence of laminin alpha-2 in the muscle biopsy.
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Congenital muscular dystrophy (CMD) is a group of rare neuromuscular disorders typically characterized by the onset of symptoms at birth or within the first two years of life. CMDs are relatively rare, but extremely severe pathological conditions currently without a safe and effective therapeutic solution. Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is among the most frequent CMDs and it is caused by mutations in the LAMA2 gene that encodes for the α2 chain of laminin-211 (merosin).
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Centre for Ecology, Evolution and Environmental Changes (CE3C) & CHANGE, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal
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