PMID: 9555046May 23, 1998Paper

T-->G or T-->A mutation introduced in the branchpoint consensus sequence of intron 4 of lecithin:cholesterol acyltransferase (LCAT) gene: intron retention causing LCAT deficiency

Biochimica Et Biophysica Acta
M LiP H Pritchard

Abstract

Previous mutations associated with lecithin:cholesteryl acyltransferase (LCAT) deficiency syndromes have been identified in the coding regions of the LCAT gene. However, recently, an intron mutation was found in a family in which three sisters presented with fish-eye disease (FED). The probands were shown to be heterozygotes for a mutation in intron 4. The respective T-->C nucleotide substitution, 22 bases upstream of the 3'-splice site, causes a null allele as the result of complete intron retention. Since the natural mutation occurs in a putative branchpoint consensus sequence of the intron, it was hypothesized that the point mutation may disrupt the splicing of the pre-mRNA. To further study the functional significance of the above thymine residue in the branchpoint sequence, we introduced other nucleotides at this position, i.e., LCAT Int-4 MUT-1 (T-->G) and LCAT Int-4 MUT-2 (T-->A). After stable transfection of the mutated pNUT-LCAT minigenes into BHK cells, we could detect neither LCAT activity nor LCAT protein in the culture medium of the pNUT-LCAT Int-4 MUT-1 and pNUT-LCAT Int-4 MUT-2 cell lines, as was previously described for the natural mutation. To determine the effects of the introduced mutations on pre-mRNA splici...Continue Reading

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Citations

Feb 21, 2008·Nucleic Acids Research·Kaiping GaoKinji Ohno
Jun 28, 2005·International Journal of Cardiology·Tiziana SampietroAlberto Bionda
Jul 13, 2006·Human Mutation·Jana KrálovicováIgor Vorechovský
Sep 1, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Julie DumontThierry Brousseau
Jan 7, 2015·Genome Research·Tim R MercerJohn S Mattick

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