Bibliographic Details
| Title: |
Abnormal splicing of ABCA1 pre-mRNA in Tangier disease due to a IVS2 +5G>C mutation in ABCA1 gene |
| Authors: |
Serena Altilia, Livia Pisciotta, Rita Garuti, Patrizia Tarugi, Alfredo Cantafora, Laura Calabresi, Jacopo Tagliabue, Sergio Maccari, Franco Bernini, Ilaria Zanotti, Carlo Vergani, Stefano Bertolini, Sebastiano Calandra |
| Source: |
Journal of Lipid Research, Vol 44, Iss 2, Pp 254-264 (2003) |
| Publisher Information: |
Elsevier, 2003. |
| Publication Year: |
2003 |
| Collection: |
LCC:Biochemistry |
| Subject Terms: |
ABCA1 minigenes, in vitro splicing, donor splice site mutation, Biochemistry, QD415-436 |
| More Details: |
Two point mutations of ABCA1 gene were found in a patient with Tangier disease (TD): i) G>C in intron 2 (IVS2 +5G>C) and ii) c.844 C>T in exon 9 (R282X). The IVS2 +5G>C mutation was also found in the brother of another deceased TD patient, but not in 78 controls and 33 subjects with low HDL. The IVS2 +5G>C mutation disrupts ABCA1 pre-mRNA splicing in fibroblasts, leading to three abnormal mRNAs: devoid of exon 2 (Ex2−/mRNA), exon 4 (Ex4−/mRNA), or both these exons (Ex2−/Ex4−/mRNA), each containing a translation initiation site. These mRNAs are expected either not to be translated or generate short peptides. To investigate the in vitro effect of IVS2 +5G>C mutation, we constructed two ABCA1 minigenes encompassing Ex1–Ex3 region, one with wild-type (WTgene) and the other with mutant (MTgene) intron 2. These minigenes were transfected into COS1 and NIH3T3, two cell lines with a different ABCA1 gene expression. In COS1 cells, WTgene pre-mRNA was spliced correctly, while the splicing of MTgene pre-mRNA resulted in Ex2−/mRNA. In NIH3T3, no splicing of MTgene pre-mRNA was observed, whereas WTgene pre-mRNA was spliced correctly.These results stress the complexity of ABCA1 pre-mRNA splicing in the presence of splice site mutations. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
0022-2275 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S0022227520312128; https://doaj.org/toc/0022-2275 |
| DOI: |
10.1194/jlr.M200248-JLR200 |
| Access URL: |
https://doaj.org/article/eb6e958ad20e4b4cb77ab5e79e99a6b5 |
| Accession Number: |
edsdoj.b6e958ad20e4b4cb77ab5e79e99a6b5 |
| Database: |
Directory of Open Access Journals |
