BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: Functional analysis is required to establish the effect of intronic mutations on ABCA1 pre-mRNA splicing.

Multiple abnormally spliced ABCA1 mRNAs caused by a novel splice site mutation of ABCA1 gene in a patient with Tangier disease / Bocchi, Letizia; Pisciotta, L; Fasano, Tommaso; Candini, Chiara; Puntoni, Mr; Sampietro, T; Bertolini, S; CALANDRA BUONAURA, Sebastiano. - In: CLINICA CHIMICA ACTA. - ISSN 0009-8981. - ELETTRONICO. - 411 (7-8)(2010), pp. 524-530.

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