A novel laminin α2 isoform in severe laminin α2 deficient congenital muscular dystrophy

Elena Pegoraro, M. Fanin, C. P. Trevisan, C. Angelini, E. P. Hoffman

Research output: Contribution to journalArticlepeer-review


Objectives: Laminin α2 deficiency presents at birth with muscle weakness, hypotonia, and usually asymptomatic white matter signal on MRI. Few patients with laminin α2 deficiency have been described with seizures and structural brain abnormalities. The reason for the variation in the severity of the clinical phenotype in congenital muscular dystrophy (CMD) with laminin α2 deficiency is not known. Methods: A patient with CMD with partial laminin α2 presenting with brain structural abnormalities and untreatable generalized and partial complex seizure was studied. Alternative laminin α2 splicing was studied by single-strand conformational polymorphism/sequencing analysis. Results: A novel laminin α2 isoform was identified. Nonsense laminin α2 mutations (stop codons) were inherited from both parents; however, one of the nonsense mutations was in a region of exon 31, which is alternatively spliced. The alternatively spliced isoform excluded one of the stop codon mutations, and was thus able to produce normal laminin α2 corresponding to this isoform. Laminin α2 immunofluorescence showed that this isoform was not evenly distributed at the muscle fiber basal lamina, but preferentially localized in discrete areas. Laminin α5, β1, γ1, and nidogen showed decreased expression by immunofluorescence. Conclusions: The severity of this patient's phenotype may be due to overexpression of the exon 31-spliced laminin α2 isoform. Exon 31 lies in the IIIA domain of the laminin α2 protein, just proximal to the triple coil-coiled region. It is possible that chain assembly is impaired by this isoform, resulting in a loss of possible rescue mechanisms.

Original languageEnglish
Pages (from-to)1128-1134
Number of pages7
Issue number8
Publication statusPublished - Oct 24 2000

ASJC Scopus subject areas

  • Neuroscience(all)


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