Format

Send to

Choose Destination
See comment in PubMed Commons below
Clin Chim Acta. 2009 May;403(1-2):131-5. doi: 10.1016/j.cca.2009.02.001. Epub 2009 Feb 7.

Splice-site mutation c.313+1, G>A in intron 3 of the LDL receptor gene results in transcripts with skipping of exon 3 and inclusion of intron 3.

Author information

1
Medical Genetics Laboratory, Department of Medical Genetics, Rikshospitalet University Hospital, Norway.

Abstract

BACKGROUND:

Familial hypercholesterolemia (FH) patients with the splice site mutation c.313+1, G>A in intron 3 of the low density lipoprotein receptor (LDLR) gene, present with a phenotype similar to that of FH patients in general. However, a mild phenotype would have been expected from the published data showing that the mutation only causes skipping of exon 3.

METHODS:

Epstein Barr virus-transformed lymphocytes from eight c.313+1, G>A heterozygotes and two c.313+1, G>A homozygotes were subjected to studies of the LDLR at the mRNA and protein levels.

RESULTS:

Mutation c.313+1, G>A not only causes skipping of exon 3, but also causes inclusion of intron 3. No functional LDLR was produced from the transcript with inclusion of intron 3. The transcript with skipping of exon 3 produced a receptor which had markedly reduced ability to internalize low density lipoprotein.

CONCLUSION:

The findings that the mutation c.313+1, G>A in the LDLR gene also generates a mutant transcript with inclusion of intron 3, explains why the mutation c.313+1, G>A may result in a severe phenotype.

PMID:
19361455
DOI:
10.1016/j.cca.2009.02.001
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center