ABCMdb

PMID: 22959828

Fasano T, Zanoni P, Rabacchi C, Pisciotta L, Favari E, Adorni MP, Deegan PB, Park A, Hlaing T, Feher MD, Jones B, Uzak AS, Kardas F, Dardis A, Sechi A, Bembi B, Minuz P, Bertolini S, Bernini F, Calandra S
Novel mutations of ABCA1 transporter in patients with Tangier disease and familial HDL deficiency.
Mol Genet Metab. 2012 Nov;107(3):534-41. doi: 10.1016/j.ymgme.2012.08.005. Epub 2012 Aug 18., [PubMed]

Sentences

No. Mutations Sentence Comment

3 ABCA1 p.His1600Arg One patient was compound heterozygous for a nucleotide insertion (c.1758_1759insG), resulting in a truncated protein and for a nucleotide substitution c.4799A>G, resulting in a missense mutation (p.H1600R). Login to comment 6 ABCA1 p.Asn1800His ABCA1 p.Arg1068Cys Three of these patients were heterozygous for known mutations (p.R130K+p.N1800H, p.R1068C, p.N1800H), while two were carriers of novel mutations (c.1195-27G>A and c.396_397insA), predicted to encode truncated proteins. Login to comment 134 ABCA1 p.His1600Arg ABCA1 p.Arg130Lys ABCA1 p.Arg1817* Mo-2 33y (M) TD 2.8 1.2 3.2 0.14 na b0.3 [c.1758_1759insG], p.R587Afs*43+[c.4799A>G], p.H1600R Mo-3 6y (F) TD 1.6 0.9 1.5 0.06 na nd [c.4465-34A>G,ins-33_-1]+[c.4465-34A>G,ins-33_-1], p.Q1488_1489insRPVCLVFM*9 Mo-4 32y (M) TD 1.3 na 2.1 0.03 0.4 b0.3 [c.4367delT]+[c.4367delT], p.M1456Sfs*45 Mo-5 6m (M) TD 2.5 0.57 1.5 0.13 na na [c.5449C>T]+[c.5449C>T], p.R1817* Mo-6 69y (F) FHD 3.7 2.7 1.5 0.3 0.97 0.4 [c.389G>A; c.5398A>C], p.R130K; p.N1800H+[wild type] Mo-7 37y (M) FHD 4.3 na 13.4 0.14 1.29 b0.3 [c.1195-27G>A,ins-25_-1], p.E398ins8V399Gfs*13+[wild type] Geߚ8 60y (F) FHD 5.6 3.6 3.5 0.72 1.16 1.0 [c.396_397insA], p.Q133Tfs*20+[wild type] Ge-9 54y (M) FHD 5.8 3.3 4.4 0.57 1.28 0.8 [c.3202C>T], p.R1068C+[wild type] Ge-10 52y (M) FHD 5.9 4.0 3.7 0.49 0.78 1.37 [c.5398A>C], p.N1800H+[wild type] TD = Tangier disease; FHD = familial HDL deficiency; y = years; m = months; M = males; F = females; na = not available, nd = not detectable. Login to comment 169 ABCA1 p.Asp1099Tyr Results 3.1. Patient # Mo-1 3.1.1. Analysis of ABCA1 gene The resequencing of the ABCA1 gene showed that this patient was heterozygous for a previously reported mutation (c.3295G>T, p.D1099Y) [19] (Table 1), predicted to be pathogenic by in silico analysis (Table 2). Login to comment 176 ABCA1 p.Asn1800His ABCA1 p.Arg1068Cys ABCA1 p.Asp1099Tyr ABCA1 p.His1600Arg ABCA1 p.His1600Arg ABCA1 p.Arg130Lys PolyPhen (PSIC score) SIFT (P score) p.R130K Possibly damaging (1.540) Predicted tolerated p.R1068C Probably damaging (3.143) Predicted not tolerated (0.00) p.D1099Y Probably damaging (3.047) Predicted not tolerated (0.00) p.H1600R Probably damaging (3.197) Predicted not tolerated (0.02) p.N1800H Possibly damaging (1.845) Predicted tolerated termination codon (p.R587Afs*43) and ii) a single nucleotide substitution (c.4799A>G) in exon 36, resulting in a novel missense mutation (p.H1600R) (Table 1). Login to comment 178 ABCA1 p.His1600Arg In silico analysis predicted that the p.H1600R mutation was probably damaging (Table 2). Login to comment 191 ABCA1 p.Arg1817* 3.5. Patient # Mo-5 3.5.1. Analysis of ABCA1 gene The patient was found to be homozygous for a single nucleotide substitution (c.5449C>T), causing the formation of a premature termination codon (p.R1817*) (Table 1). Login to comment 193 ABCA1 p.Asn1800His ABCA1 p.Arg130Lys 3.6. Patient # Mo-6 3.6.1. Analysis of ABCA1 gene This patient was a carrier of two single nucleotide substitutions: i) c.389G>A resulting in the conversion of arginine to lysine (p.R130K) predicted in silico to be benign and ii) c.5398A>C resulting in a previously reported missense mutation (p.N1800H) [8], predicted in silico to be possibly damaging (Table 2). Login to comment 222 ABCA1 p.Arg1068Cys 3.9. Patient # Ge-9 3.9.1. Analysis of ABCA1 gene This patient was found to be heterozygous for a missense mutation (c.3202C>T, p.R1068C), previously described in a compound heterozygous patient [20]. Login to comment 223 ABCA1 p.Arg1068Cys In silico analysis predicted that the p.R1068C mutation was probably damaging (Table 2). Login to comment 224 ABCA1 p.Asn1800His 3.10. Patient # Ge-10 3.10.1. Analysis of ABCA1 gene This patient was heterozygous for a mutation (c.5398A>C, p.N1800H), previously reported in patients with hypoalphalipoproteinemia [8] and found in another patient with low HDL of our series (patient # Mo-6). Login to comment 235 ABCA1 p.Asp1099Tyr The alternative hypothesis is that the missense mutation (p.D1099Y) found in this patient has a dominant negative effect. Login to comment 236 ABCA1 p.Phe2009Ser This hypothesis is unlikely in view of the fact that this mutation was originally reported by Ho Hong et al. [19] in one patient with extremely low plasma HDL-C and ApoA-I (4 and 8 mg/dL respectively, consistent with the diagnosis of TD) who was in fact a compound heterozygote, carrying another missense mutation (p.F2009S), which segregated with low plasma HDL-C phenotype in the patient's pedigree. Login to comment