Mild muscular dystrophy due to a nonsense mutation in the LAMA2 gene resulting in exon skipping

Claudia Di Blasi, Yi He, Lucia Morandi, Ferdinando Cornelio, Pascale Guicheney, Marina Mora

Research output: Contribution to journalArticle

Abstract

Nonsense mutations outside the splicing consensus sequence have been reported to cause skipping of the nonsense-containing exon in several human diseases. We describe, for the first time, nonsense-mediated exon skipping in the laminin α2 (LAMA2) gene. Two siblings from a consanguineous family had altered expression of the laminin α2 chain and moderate clinical manifestations. In both we identified the new nonsense mutation Arg744Stop, which we expected to result in a totally non-functional polypeptide. However, analysis of the transcript revealed skipping of exon 15, containing the mutation, even though the consensus sequences for splicing at both ends of the exon and the beginning of intron 15 were unaltered. Exon skipping restored the open reading frame of the mutant transcript and resulted in a truncated protein. In cases where the genetic findings do not elucidate the phenotype, mRNA analysis is necessary to clarify the primary effect of mutations. Our findings also point to the necessity of immunochemical screening for expression of laminin α2 chain in atypical dystrophic adults as well as children.

Original languageEnglish
Pages (from-to)698-704
Number of pages7
JournalBrain
Volume124
Issue number4
Publication statusPublished - 2001

Fingerprint

Muscular Dystrophies
Nonsense Codon
Exons
Laminin
Genes
Consensus Sequence
Mutation
Introns
Open Reading Frames
Siblings
Phenotype
Messenger RNA
Peptides
Proteins

Keywords

  • Congenital muscular dystrophy
  • LAMA2
  • Laminin α2 chain
  • Merosin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Di Blasi, C., He, Y., Morandi, L., Cornelio, F., Guicheney, P., & Mora, M. (2001). Mild muscular dystrophy due to a nonsense mutation in the LAMA2 gene resulting in exon skipping. Brain, 124(4), 698-704.

Mild muscular dystrophy due to a nonsense mutation in the LAMA2 gene resulting in exon skipping. / Di Blasi, Claudia; He, Yi; Morandi, Lucia; Cornelio, Ferdinando; Guicheney, Pascale; Mora, Marina.

In: Brain, Vol. 124, No. 4, 2001, p. 698-704.

Research output: Contribution to journalArticle

Di Blasi, C, He, Y, Morandi, L, Cornelio, F, Guicheney, P & Mora, M 2001, 'Mild muscular dystrophy due to a nonsense mutation in the LAMA2 gene resulting in exon skipping', Brain, vol. 124, no. 4, pp. 698-704.
Di Blasi C, He Y, Morandi L, Cornelio F, Guicheney P, Mora M. Mild muscular dystrophy due to a nonsense mutation in the LAMA2 gene resulting in exon skipping. Brain. 2001;124(4):698-704.
Di Blasi, Claudia ; He, Yi ; Morandi, Lucia ; Cornelio, Ferdinando ; Guicheney, Pascale ; Mora, Marina. / Mild muscular dystrophy due to a nonsense mutation in the LAMA2 gene resulting in exon skipping. In: Brain. 2001 ; Vol. 124, No. 4. pp. 698-704.
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