Cristin-resultat-ID: 915855
Sist endret: 12. august 2013 14:56
NVI-rapporteringsår: 2011
Resultat
Vitenskapelig artikkel
2011

Exon trapping analysis of c.301-19G > A in intron 1 of the SHH gene in a patient with a microform of holoprosencephaly

Bidragsytere:
  • Mari Ann Kulseth
  • Robert Lyle
  • Olaug Kristin Rødningen
  • Hanne Sørmo Sorte og
  • Trine Prescon

Tidsskrift

European Journal of Medical Genetics
ISSN 1769-7212
e-ISSN 1878-0849
NVI-nivå 1

Om resultatet

Vitenskapelig artikkel
Publiseringsår: 2011
Volum: 54
Hefte: 2
Sider: 130 - 135

Importkilder

Isi-ID: 000293744000006

Beskrivelse Beskrivelse

Tittel

Exon trapping analysis of c.301-19G > A in intron 1 of the SHH gene in a patient with a microform of holoprosencephaly

Sammendrag

It can be difficult to assess the clinical significance of novel genomic sequence variants which may potentially alter mRNA splicing. Segregation analysis is not helpful in isolated cases or small families. Bioinformatic tools can provide additional information, but direct analysis of mRNA from an appropriate tissue remains the preferred approach for analyzing the effect of a sequence variant on splicing. However, hundreds of disease-associated and developmental genes, including the Sonic Hedgehog homolog (SHH) gene, are not expressed in blood or fibroblasts postnatally. We identified a de novo nucleotide change, c.301-19G > A, in intron 1 of SHH in a four year old boy with a microform of holoprosencephaly. In silico analyses predicted unaltered splicing. We used a minigene approach to study the variant more closely. The genomic region of interest was inserted into an exon trapping vector to create an artificial pre-mRNA in transfected cells. We found virtually complete inactivation of the splice acceptor site in intron 1 in two different transfected cell lines. In light of the clinical context, the de novo nature of the substitution and the results of the exon trapping analyses, we conclude that the detected variant is pathogenic and that the recurrence risk for sibs is low. This case demonstrates that in the absence of a readily available mRNA source, exon trapping can be a robust and practical aid in clinical practice for assessing the effect of genomic variants on pre-mRNA splicing.

Bidragsytere

Mari Ann Kulseth

  • Tilknyttet:
    Forfatter
    ved Avdeling for medisinsk genetikk ved Oslo universitetssykehus HF

Robert Lyle

  • Tilknyttet:
    Forfatter
    ved Avdeling for medisinsk genetikk ved Oslo universitetssykehus HF

Olaug Kristin Rødningen

  • Tilknyttet:
    Forfatter
    ved Avdeling for medisinsk genetikk ved Oslo universitetssykehus HF

Hanne Sørmo Sorte

  • Tilknyttet:
    Forfatter
    ved Avdeling for medisinsk genetikk ved Oslo universitetssykehus HF

Trine Prescott

Bidragsyterens navn vises på dette resultatet som Trine Prescon
  • Tilknyttet:
    Forfatter
    ved Avdeling for medisinsk genetikk ved Oslo universitetssykehus HF
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