ABCA1 p.Arg557*
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[hide] Familial HDL deficiency due to ABCA1 gene mutation... Atherosclerosis. 2004 Feb;172(2):309-20. Pisciotta L, Hamilton-Craig I, Tarugi P, Bellocchio A, Fasano T, Alessandrini P, Bon GB, Siepi D, Mannarino E, Cattin L, Averna M, Cefalu AB, Cantafora A, Calandra S, Bertolini S
Familial HDL deficiency due to ABCA1 gene mutations with or without other genetic lipoprotein disorders.
Atherosclerosis. 2004 Feb;172(2):309-20., [PMID:15019541]
Abstract [show]
Mutations in ABCA1 have been shown to be the cause of Tangier disease (TD) and some forms of familial hypoalphalipoproteinemia (HA), two genetic disorders characterized by low plasma HDL levels. Here we report six subjects with low HDL, carrying seven ABCA1 mutations, six of which are previously unreported. Two mutations (R557X and H160FsX173) were predicted to generate short truncated proteins; two mutations (E284K and Y482C) were located in the first extracellular loop and two (R1901S and Q2196H) in the C-terminal cytoplasmic domain of ABCA1. Two subjects found to be compound heterozygotes for ABCA1 mutations did not have overt clinical manifestations of TD. Three subjects, all with premature coronary artery disease (pCAD), had a combination of genetic defects. Besides being heterozygotes for ABCA1 mutations, two of them were also carriers of the R3500Q substitution in apolipoprotein B and the third was a carrier of N291S substitution in lipoprotein lipase. By extending family studies we identified 17 heterozygotes for ABCA1 mutations. Plasma HDL-C and Apo A-I values in these subjects were 38.3 and 36.9% lower than in unaffected family members and similar to the values found in heterozygotes for Apo A-I gene mutations which prevent Apo A-I synthesis. This survey underlines the allelic heterogeneity of ABCA1 mutations and suggests that: (i) TD subjects, if asymptomatic, may be overlooked and (ii) there may be a selection bias in genotyping towards carriers of ABCA1 mutations who have pCAD possibly related to a combination of genetic and environmental cardiovascular risk factors.
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No. Sentence Comment
2 Two mutations (R557X and H160FsX173) were predicted to generate short truncated proteins; two mutations (E284K and Y482C) were located in the first extracellular loop and two (R1901S and Q2196H) in the C-terminal cytoplasmic domain of ABCA1.
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ABCA1 p.Arg557* 15019541:2:15
status: NEW70 The proband of Family 5 was a carrier of an ABCA1 mutation (R557X) and an Apo B mutation (R3500Q).
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ABCA1 p.Arg557* 15019541:70:60
status: NEW123 Transition c.1669 C > T in exon 13 (R557X) As this mutation introduces a Bgl II restriction site, a 333 bp PCR fragment encompassing exon 13 was digested with Bgl II (Amersham Pharmacia Biotech, Cologno Monzese, Italy).
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ABCA1 p.Arg557* 15019541:123:36
status: NEW164 II.2 W/W 43 M 28.0 5.10 3.70 0.96 0.80 104 98 ε3ε4 III.3 M2/W 9 M - 3.00 1.94 0.75 0.70 92 52 ε3ε4 Family 4 II.1 M4/W 62 M 23.3 4.45 2.71 0.72 2.21 102 92 ε3ε3 +++ Family 5 II.1a M5/W 59 M 36.7 7.16 6.02 0.52 1.71 81 133 ε3ε4 +++ III.1a W/W 33 F 21.8 7.52 5.02 1.99 1.13 162 112 ε4ε4 III.2 M5/W 31 F 22.8 4.68 3.28 0.85 1.18 92 82 ε3ε4 III.3 M5/W 31 F 24.4 4.00 2.74 0.90 0.78 97 72 ε3ε4 Family 6 I.2 M6/W 53 F 40.2 4.76 3.00 1.16 1.31 104 81 ε3ε3 II.1 W/W 41 M 27.5 6.54 4.35 1.19 2.20 141 148 ε3ε4 II.2 M6/W 39 M 26.2 3.57 2.44 0.77 0.77 93 71 ε3ε4 II.3 M6/W 37 F 21.3 4.44 2.63 0.76 2.30 85 89 ε3ε4 II.4 M7/W 37 M 18.8 3.67 2.43 1.00 0.50 89 57 ε3ε3 III.1 M6/M7 16 F 25.4 3.33 2.45 0.18 1.55 12 102 ε3ε3 III.2 M7/W 10 F 14.2 2.66 1.34 0.98 0.76 103 38 ε3ε3 W, ABCA1 wild-type allele; M, ABCA1 mutant allele: M1 (E284K); M2 (N1800H); M3 (Y482C); M4 (Q2196H); M5 (R557X); M6 (H160FsX173); M7 (R1901S); ND: not determined.
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ABCA1 p.Arg557* 15019541:164:1005
status: NEWX
ABCA1 p.Arg557* 15019541:164:1033
status: NEW172 The sequence of ABCA1 gene revealed that the proband was heterozygous for a transition c.1669 C > T (R557X) in exon 13 (Fig. 4); this mutation was also present in proband`s twin daughters.
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ABCA1 p.Arg557* 15019541:172:101
status: NEW200 of our series (Families 2 and 3), we are tempted to suggest that N1800H might be a recurrent mutation.
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ABCA1 p.Arg557* 15019541:200:63
status: NEW201 The novel mutations we identified included: (a) one non-sense (R557X) and one frameshift (H160FsX173) mutation, both predicted to encode short peptides presumably devoid of any function; (b) four missense mutations (E284K, Y482C, R1901S and Q2196H) resulting in non-homologous amino acid substitutions.
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ABCA1 p.Arg557* 15019541:201:63
status: NEW