ABCMdb

PMID: 12576507

Altilia S, Pisciotta L, Garuti R, Tarugi P, Cantafora A, Calabresi L, Tagliabue J, Maccari S, Bernini F, Zanotti I, Vergani C, Bertolini S, Calandra S
Abnormal splicing of ABCA1 pre-mRNA in Tangier disease due to a IVS2 +5G>C mutation in ABCA1 gene.
J Lipid Res. 2003 Feb;44(2):254-64. Epub 2002 Nov 4., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCA1 p.Arg282* Copyright (c) 2003 by Lipid Research, Inc. 254 Journal of Lipid Research Volume 44, 2003 This article is available online at http://www.jlr.org Abnormal splicing of ABCA1 pre-mRNA in Tangier disease due to a IVS2 5GC mutation in ABCA1 gene Serena Altilia,* Livia Pisciotta,ߤ Rita Garuti,* Patrizia Tarugi,* Alfredo Cantafora,&#a7; Laura Calabresi,** Jacopo Tagliabue,ߤߤ Sergio Maccari,&#a7;&#a7; Franco Bernini,*** Ilaria Zanotti,*** Carlo Vergani,ߤߤ Stefano Bertolini,ߤ and Sebastiano Calandra1,** Department of Biomedical Sciences,* University of Modena and Reggio Emilia; Department of Internal Medicine,ߤ University of Genoa; National Institute of Health,&#a7; Rome; Department of Pharmacological Sciences,** Center "E. Grossi Paoletti," University of Milan; Ospedale Maggiore-IRCCS,ߤߤ Milan; Sant`Anna Hospital,&#a7;&#a7; Castelnuovo Monti, Reggio Emilia; and Departments of Pharmacological*** and Biological Sciences and Applied Chemistries, University of Parma, Italy Abstract Two point mutations of ABCA1 gene were found in a patient with Tangier disease (TD): i) GC in intron 2 (IVS2 5GC) and ii) c.844 CT in exon 9 (R282X). Login to comment 1 ABCA1 p.Arg282* 254 Journal of Lipid Research Volume 44, 2003 This article is available online at http://www.jlr.org Abnormal splicing of ABCA1 pre-mRNA in Tangier disease due to a IVS2 ϩ5GϾC 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,† and Sebastiano Calandra1,** Department of Biomedical Sciences,* University of Modena and Reggio Emilia; Department of Internal Medicine,† University of Genoa; National Institute of Health,§ Rome; Department of Pharmacological Sciences,** Center "E. Grossi Paoletti," University of Milan; Ospedale Maggiore-IRCCS,†† Milan; Sant`Anna Hospital,§§ Castelnuovo Monti, Reggio Emilia; and Departments of Pharmacological*** and Biological Sciences and Applied Chemistries, University of Parma, Italy Abstract Two point mutations of ABCA1 gene were found in a patient with Tangier disease (TD): i) GϾC in intron 2 (IVS2 ؉5GϾC) and ii) c.844 CϾT in exon 9 (R282X). Login to comment 78 ABCA1 p.Arg282* The R282X mutation and the cosegregating haplotype are indicated by red color (see sequence analysis in Fig. 3). Login to comment 79 ABCA1 p.Arg282* The R282X mutation and the cosegregating haplotype are indicated by red color (see sequence analysis in Fig. 3). Login to comment 157 ABCA1 p.Arg587Trp The cholesterol efflux in proband`s fibroblasts was similar to that observed in another patient with TD (homozygous for R587W in ABCA1 gene) we have previously reported (13) (Fig. 2). Login to comment 158 ABCA1 p.Arg587Trp The cholesterol efflux in proband`s fibroblasts was similar to that observed in another patient with TD (homozygous for R587W in ABCA1 gene) we have previously reported (13) (Fig. 2). Login to comment 164 ABCA1 p.Arg282* The sequence of ABCA1 gene revealed that proband I.1 (Family 1) was a compound heterozygote for: i) a GC transversion at the 5th nucleotide of intron 2 (IVS2 5GC), and ii) a c.844 CT transition in exon 9, which converts the arginine codon at position 282 into a termination codon (R282X) (Fig. 3). Login to comment 165 ABCA1 p.Arg282* The sequence of ABCA1 gene revealed that proband I.1 (Family 1) was a compound heterozygote for: i) a GϾC transversion at the 5th nucleotide of intron 2 (IVS2 ϩ5GϾC), and ii) a c.844 CϾT transition in exon 9, which converts the arginine codon at position 282 into a termination codon (R282X) (Fig. 3). Login to comment 167 ABCA1 p.Arg282* The c.844 CT mutation (R282X) introduces a new AflIII restriction site. Login to comment 168 ABCA1 p.Arg282* The c.844 CϾT mutation (R282X) introduces a new AflIII restriction site. Login to comment 169 ABCA1 p.Arg282* The proband`s brother was heterozygous for the nonsense mutation in exon 9 (R282X). Login to comment 170 ABCA1 p.Arg282* The proband`s brother was heterozygous for the nonsense mutation in exon 9 (R282X). Login to comment 173 ABCA1 p.Arg282* Haplotype analysis The genotyping of five polymorphic markers close to or within the ABCA1 gene demonstrated: i) the IVS2 5GC mutation co-segregates with haplotype a; ii) the probands of Family 1 and Family 2 share this haplotype; iii) the nonsense mutation (R282X) cosegregates with haplotype b (Fig. 1). Login to comment 174 ABCA1 p.Arg282* Haplotype analysis The genotyping of five polymorphic markers close to or within the ABCA1 gene demonstrated: i) the IVS2 ϩ5GϾC mutation co-segregates with haplotype a; ii) the probands of Family 1 and Family 2 share this haplotype; iii) the nonsense mutation (R282X) cosegregates with haplotype b (Fig. 1). Login to comment 178 ABCA1 p.Arg587Trp ABCA1 p.Arg282* Skin fibroblasts from a control subject, proband I.1 of Family 1 (IVS2 5GC/ R282X), and another TD patient (homozygous for R587W) reported previously (13) were labeled with [3H]cholesterol and then incubated in the presence or in the absence of 22-hydroxycholesterol and 9-cis-retinoic acid (22ch/RA). Login to comment 179 ABCA1 p.Arg587Trp ABCA1 p.Arg282* Skin fibroblasts from a control subject, proband I.1 of Family 1 (IVS2 ϩ5GϾC/ R282X), and another TD patient (homozygous for R587W) reported previously (13) were labeled with [3H]cholesterol and then incubated in the presence or in the absence of 22-hydroxycholesterol and 9-cis- retinoic acid (22ch/RA). Login to comment 184 ABCA1 p.Arg282* Analysis of cDNA Unexpectedly, the sequence of the cDNA region encompassing exons 5-10 failed to confirm the presence of the c.844 CT (R282X) mutation in exon 9 in proband I.1 (Family 1), suggesting that only one mutant allele was expressed in fibroblasts. Login to comment 185 ABCA1 p.Arg282* Analysis of cDNA Unexpectedly, the sequence of the cDNA region encompassing exons 5-10 failed to confirm the presence of the c.844 CϾT (R282X) mutation in exon 9 in proband I.1 (Family 1), suggesting that only one mutant allele was expressed in fibroblasts. Login to comment 210 ABCA1 p.Arg282* ABCA1 cDNA region spanning from exon 5 to exon 10 was amplified by PCR and digested with Af l III to detect the c.844 CT mutation (R282X) in exon 9. Login to comment 211 ABCA1 p.Arg282* ABCA1 cDNA region spanning from exon 5 to exon 10 was amplified by PCR and digested with Af l III to detect the c.844 CϾT mutation (R282X) in exon 9. Login to comment 273 ABCA1 p.Arg282* One of the mutations found in proband I.1 (Family 1) is a nonsense mutation in exon 9 (R282X) that involves a CpG dinucleotide, a well-recognized hot spot for base substitution (39). Login to comment 274 ABCA1 p.Arg282* One of the mutations found in proband I.1 (Family 1) is a nonsense mutation in exon 9 (R282X) that involves a CpG dinucleotide, a well-recognized hot spot for base substitution (39). Login to comment