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 language | English |
|---|---|
| Pages (from-to) | 698-704 |
| Number of pages | 7 |
| Journal | Brain |
| Volume | 124 |
| Issue number | 4 |
| Publication status | Published - 2001 |
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Keywords
- Congenital muscular dystrophy
- LAMA2
- Laminin α2 chain
- Merosin
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Mild muscular dystrophy due to a nonsense mutation in the LAMA2 gene resulting in exon skipping
AU - Di Blasi, Claudia
AU - He, Yi
AU - Morandi, Lucia
AU - Cornelio, Ferdinando
AU - Guicheney, Pascale
AU - Mora, Marina
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Congenital muscular dystrophy
KW - LAMA2
KW - Laminin α2 chain
KW - Merosin
UR - http://www.scopus.com/inward/record.url?scp=0035051754&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035051754&partnerID=8YFLogxK
M3 - Article
C2 - 11287370
AN - SCOPUS:0035051754
VL - 124
SP - 698
EP - 704
JO - Brain
JF - Brain
SN - 0006-8950
IS - 4
ER -