ABCMdb

ABCC6 p.Gln655Arg

LOVD-ABCC6:	p.Gln655Arg D
Predicted by SNAP2:	A: N (66%), C: N (78%), D: N (53%), E: N (93%), F: N (53%), G: D (53%), H: N (72%), I: N (57%), K: N (97%), L: N (53%), M: N (66%), N: N (61%), P: N (82%), R: N (93%), S: N (87%), T: N (72%), V: N (66%), W: D (53%), Y: N (53%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: N, F: D, G: D, H: D, I: D, K: N, L: D, M: D, N: D, P: D, R: N, S: D, T: D, V: D, W: D, Y: D,

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Publications
[hide] Analysis of sequence variations in the ABCC6 gene ... J Vasc Res. 2005 Sep-Oct;42(5):424-32. Epub 2005 Aug 26. Schulz V, Hendig D, Schillinger M, Exner M, Domanovits H, Raith M, Szliska C, Kleesiek K, Gotting C
Analysis of sequence variations in the ABCC6 gene among patients with abdominal aortic aneurysm and pseudoxanthoma elasticum.
J Vasc Res. 2005 Sep-Oct;42(5):424-32. Epub 2005 Aug 26., [PMID:16127278]

Abstract [show]
Abdominal aortic aneurysm (AAA) is characterized by dilatation of arterial walls, which is accompanied by degradation of elastin and collagen molecules. Biochemical and environmental factors are known to be relevant for AAA development, and familial predisposition is well recognized. A connective tissue disorder that is also associated with fragmentation of elastic fibers is Pseudoxanthoma elasticum (PXE). PXE is caused by mutations in the ABCC6 gene and mainly affects dermal, ocular and all vascular tissues. To investigate whether variations in ABCC6 are found in AAA patients and to determine mutations in PXE patients, we analyzed seven selected ABCC6 exons of 133 AAA and 54 PXE patients subjected to mutational analysis. In our cohort of AAA patients, we found five ABCC6 alterations, which result in missense or silent amino acid variants. The allelic frequencies of these sequence variations were not significantly different between AAA patients and healthy controls. Therefore, we suggest that alterations in ABCC6 are not a genetic risk factor for AAA. Mutational screening of the PXE patients revealed 19 different ABCC6 variations, including two novel PXE-causing mutations. These results expand the ABCC6 mutation database in PXE.

Comments [show]

This is erroneously identified as a reported sequence variant. In the cited article E18L is the name of a PCR primer.
aranyi on 2012-05-05 13:15:49

Sentences [show]
No. Sentence Comment
97 These sequence variations led to the missense and silent amino acid variants p.Q655R, p.R724K, p.V725V, p.I742V and p.R1418R. Login to comment
98 The p.Q655R mutation occurred in a heterozygous state in one AAA patient and was absent in our PXE cohort and in 143 control subjects. Login to comment
113 Novel ABCC6 Sequence Alterations Among the 22 ABCC6 sequence variations found in this study, 17 had been previously described as PXE-causing mutations and ABCC6 polymorphisms [16, 19, 22-24, 30, 35, 36], and 5 were novel DNA alterations resulting in the missense and silent variants p.Q655R, p.P664S, p.R1114C, p.G1311E and p.R1418R. Login to comment
116 The variations p.R1114C and p.G1311E occurred in a heterozygous form in 2 PXE patients, and RFLP or DHPLC analysis revealed that they were not present in our groups of healthy controls Exona Sequence variation Allele frequency AAA patients PXE patients PXE relatives blood donors 16 c.1964A>G (p.Q655R) 1 0 0 0/286 16 c.1990C>T (p.P664S) 0 0 0 1/286 16 c.1995delG (frameshift) 0 3 0 0/286 17 c.2171G>A (p.R724K) 3 1 1 2/254 17 c.2175A>T (p.V725V) 3 1 1 2/254 17 c.2224A>G (p.I742V) 3 1 1 2/254 i-17 IVS17+22T>G 1 0 0 0/254 18 c.2252T>A (p.M751K) 0 2 0 0/204 18 c.2278C>T (p.R760W) 0 1 0 0/204 18 c.2294G>A (p.R765Q) 0 3 0 0/204 24 c.3340C>T (p.R1114C) 0 1 0 0/400 24 c.3341G>A (p.R1114H) 0 1 0 0/400 24 c.3389C>T (p.T1130M) 0 2 0 0/400 24 c.3413G>A (p.R1138Q) 0 2 0 ND 24 c.3421C>T (p.R1141X) 0 28 9 1/1,820b i-24 IVS24+15G>A 1 0 0 ND 28 c.3902C>T (p.T1301I) 0 1 0 ND 28 c.3932G>A (p.G1311E) 0 1 0 0/400 28 c.3940C>T (p.R1314W) 0 1 0 ND 28 c.3941G>A (p.R1314Q) 0 1 1 ND i-28 IVS28+49C>T 59 ND ND ND i-28 IVS28-30C>T 48 ND ND ND 29 c.4182delG (frameshift) 0 3 0 0/400 i-29 IVS29+9G>A 5 ND ND ND 30 c.4209C>A (p.S1403R) 0 1 0 0/244 30 c.4254G>A (p.R1418R) 6 0 0 2/244 i-30 IVS30+11C>G 0 2 0 0/244 23-29 Ex23_Ex29del 0 5 3 ND i = intron; ND = not determined. Login to comment
124 The p.Q655R and p.P664S mutations were identified in a heterozygous state in only 1 AAA patient and 1 control subject, respectively. Login to comment
147 The mutation p.Q655R was identified in a heterozygous form in 1 AAA patient who was found to bear no other mutation in the coding region of the ABCC6 gene, including the frequent PXE mutation Ex23_ Ex29del. Login to comment
149 Consequently, the potential cosegregation of p.Q655R with AAA formation could not be analyzed in the present study and supply information about the pathogenicity of this mutation. Login to comment
150 Among healthy controls, p.Q655R was absent, but the difference in the allelic frequencies in AAA patients and controls was not statistically significant. Login to comment
151 Therefore, we suppose the p.Q655R mutation not to be pathogenic, although there is still the possibility that the heterozygous p.Q655R variant may play a role in AAA development. Login to comment