Abnormal splicing of ABCA1 pre-mRNA in Tangier disease due to a IVS2 +5G>C mutation in ABCA1 gene

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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)254-264
Number of pages11
JournalJournal of Lipid Research
Issue number2
Publication statusPublished - Feb 2003


  • ABCA1 minigenes
  • Donor splice site mutation
  • In vitro splicing

ASJC Scopus subject areas

  • Endocrinology


Dive into the research topics of 'Abnormal splicing of ABCA1 pre-mRNA in Tangier disease due to a IVS2 +5G>C mutation in ABCA1 gene'. Together they form a unique fingerprint.

Cite this