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Clin Chim Acta. 2010 Apr 2;411(7-8):524-30. doi: 10.1016/j.cca.2010.01.008. Epub 2010 Jan 20.

Multiple abnormally spliced ABCA1 mRNAs caused by a novel splice site mutation of ABCA1 gene in a patient with Tangier disease.

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Department of Biomedical Sciences, University of Modena and Reggio Emilia, Italy.



Mutations in ABCA1 gene are the cause of Tangier disease (TD) and familial high density lipoprotein (HDL) deficiency. Splice site mutations of this gene were reported infrequently.


ABCA1 gene was sequenced in a TD patient and in subjects with low HDL. The effect of intronic variants on ABCA1 pre-mRNA splicing was studied in COS-1 cells expressing a mutant minigene or in patients' cells.


A novel mutation in intron 20 (c.2961 -2 A>C) was found in the TD patient. To assess its effect, a mutant ABCA1 minigene, containing intron 18-intron 23 region, was expressed in COS-1 cells. The mutant minigene generated three transcripts: i) in the first (459bp) 61 nucleotides of intron 20 were retained; ii) in the second (384bp) exon 20 joined to exon 21 devoid of the first 14 nucleotides; and iii) in the third (255bp) the entire exon 21 was skipped. The first two transcripts were also observed in patient's peripheral blood mononuclear cells. These mRNAs encode truncated proteins. A variant in intron 8 (c.814 -14 ins A), identified in subjects with low HDL, had no effect on ABCA1 pre-mRNA splicing.


Functional analysis is required to establish the effect of intronic mutations on ABCA1 pre-mRNA splicing.

[Indexed for MEDLINE]

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