ABCMdb

ABCC6 p.Arg1268Gln

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Publications

PMID: 16006996 [PubMed] Conseil G et al: "Polymorphisms of MRP1 (ABCC1) and related ATP-dependent drug transporters."

No. Sentence Comment

56 In the kidney, glomeruli and distal collecting tubules express MRP1, and, in the brain, MRP1 appears to form part of the drug permeability barrier Fig. 1 CF (CFTR/ABCC7) Q1291R E1228G Q1238R G1244E/V G1247R G1249R S1251N S1255P/L W1282G/R/C R1283K/M N1303K Y1307C E1321Q K1351E Q1352H R1268Q V1298F T1301I G1302R A1303P R1314W/Q G1321S R1339C Q1347H I1350L G1354R D1361N Q1382R A1450T R1347E R1351P V1359G/M S1368A G1377R G1382S R1392H R1419C R1435Q G1477R G1479R R1492W E1505K DJS (MRP2/ABCC2) NBD1 NBD2 COOH MEMBRANE MSD MSD MSD 12131415161710116 7 8 91 23 4 5TM H2 N Extracellular Intracellular PXE (ABCC6) PHHI (SUR1/ABCC8) Two-dimensional structure of MRP-related proteins. Login to comment

PMID: 10811882 [PubMed] Ringpfeil F et al: "Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter."

No. Sentence Comment

75 The mutation in exon 27 resulted in substitution of a codon for arginine by a codon for glutamine (R1268Q). Login to comment
77 MRP6 mutations in families with PXE Family Age and sex of proband Mutation Exon Consequence Verification* 1 53 F 3421C 3 T 24 R1141X BsiYI 3803G 3 A 27 R1268Q BstXI 2 29 F 3412C 3 T 24 R1138W MspI 3 40 F 3421C 3 T 24 R1141X BsiYI Partial deletion 24† Allelic loss D16S2720 MRP6 D16B9622 4 53 F 3736-1G 3 A 27 Altered splicing of exon 27 AciI Partial deletion 27† Allelic loss D16S2720 MRP6 D16B9622 5 60 M 3413G 3 A 24 R1138Q MspI 3803G 3 A 27 R1268Q BstXI 6 28 F 3421C 3 T 24 R1141X BsiYI 7 41 M 3803G 3 A 27 R1268Q BstXI 8 25 F 3421C 3 T 24 R1141X BsiYI *Mutations were verified in the proband and his/her family members by digestion with restriction enzyme, or in case of deletion, by microsatellite markers indicated. Login to comment
142 Evaluation of their DNA revealed that the patient in family 5 was compound heterozygous for nucleotide substitutions 3413G3A and 3803G3A in exons 24 and 27, which resulted in the amino acid substitutions R1138Q and R1268Q, respectively. In families 6-8, heterozygous nucleotide substitutions were discovered, resulting in the mutations R1141X (families 6 and 8), and R1268Q (family 7). Login to comment
159 Although only one mutation in each of the latter three individuals was observed, it is likely that PXE in these cases was also autosomal recessive, because each of the two distinct mutations (R1141X and R1268Q) discovered in these three probands were also present in the multiplex families, and the heterozygous carriers did not show definitive signs of the disease. Login to comment

PMID: 10913334 [PubMed] Germain DP et al: "Homozygosity for the R1268Q mutation in MRP6, the pseudoxanthoma elasticum gene, is not disease-causing."

No. Sentence Comment

0 Homozygosity for the R1268Q Mutation in MRP6, the Pseudoxanthoma Elasticum Gene, Is Not Disease-Causing Dominique P. Germain,1 Je´roˆme Perdu, Ve´ronique Remones, and Xavier Jeunemaitre De´partement de Ge´ne´tique, Hoˆpital Europe´en Georges Pompidou, Universite´ Paris VI, Paris, France Received June 13, 2000 Pseudoxanthoma elasticum (PXE) is an inherited systemic disorder of connective tissue, characterized by progressive calcification of the elastic fibers in the eye, the skin, and the cardiovascular system, resulting in decreased vision, skin lesions, and life-threatening vascular disease, with highly variable phenotypic expression. Login to comment
4 In one large PXE pedigree for which we had identified a nonsense mutation (R1141X), we came across a G to A transition at position 3803 of the MRP6 cDNA sequence (R1268Q). Login to comment
6 We investigated the R1268Q mutation, and found the Q1268 allele at a relatively high frequency (0.19) in a Caucasian control population (n ‫؍‬ 62 subjects). Login to comment
8 These data indicate that the R1268Q variant in the MRP6 gene does not cause PXE per se. Login to comment
18 During our molecular analysis of the MRP6 gene in PXE patients, we came across a G to A transition at position 3803 of the cDNA sequence, altering the codon (CGG) for arginine to the codon (CAG) for glutamine (R1268Q) in a pedigree in which we had previously identified a nonsense mutation (R1141X). Login to comment
19 In the present study, the R1268Q mutation was investigated in relatives of our PXE patients and in a control population, to determine if this amino-acid change was a disease-causing mutation or a neutral polymorphism. Login to comment
39 Mutation R1268Q predicted the creation of a novel restriction site for BstX I. Login to comment
42 Mutation R1268Q also predicted the loss of a Msp I restriction site. Login to comment
51 This nucleotide substitution alters the codon (CGG) for arginine to the codon (CAG) for glutamine (R1268Q). Login to comment
52 Restriction digests using BstX I, performed to examine family relatives, showed that both affected patients (II-3 and II-5) and their asymptomatic mother (I-2) were heteroallelic for R1268Q at the genomic level, the father (I-1) being a wild type homozygote. Login to comment
53 However, the proband`s asymptomatic husband (individual II-6 in Fig. 1) was found to be homozygote for R1268Q, ruling out a causative role for homozygosity for this mutation in the clinical phenotype observed in PXE patients. Login to comment
54 Mutation R1268Q also predicted the loss of a Msp I restriction site. Login to comment
57 The R1268Q mutation was identified in 24 of the 124 tested alleles, and its overall frequency was 0.19 (Fig. 3). Login to comment
60 Our results indicate that the R1268Q mutation in the MRP6 gene is a neutral polymorphism, which does not cause pseudoxanthoma elasticum when present at the homozygous state. Login to comment
66 During our mutational scanning of the MRP6 gene, in two sisters affected with pseudoxanthoma elasticum, a G to A transition, was detected at position 3803 of the MRP6 cDNA sequence, predicting a R1268Q missense mutation at the protein level. Login to comment
98 We have therefore investigated the R1268Q substitution to determine its frequency, and have found its frequency to be high in a Caucasian control population. Login to comment
100 It is interesting to note that the authors also detected the R1268Q mutation in their patients population, although always in the context of compound heterozygosity. Login to comment
101 Whether the R1268Q mutation may lead to the clinical phenotype observed in patients with PXE, when found in association with another, potentially more severe, mutation in the MRP6 gene remains to be elucidated. Login to comment
103 In conclusion, while screening the MRP6 gene in patients affected with PXE, we have identified, beside disease-causing mutations, a 3803G Ͼ A transition (R1268Q) which was shown to be a harmless polymorphism when present at the homozygous state. Login to comment

PMID: 11179012 [PubMed] Ringpfeil F et al: "Compound heterozygosity for a recurrent 16.5-kb Alu-mediated deletion mutation and single-base-pair substitutions in the ABCC6 gene results in pseudoxanthoma elasticum."

No. Sentence Comment

214 Proc Natl Acad Sci USA 90:10325-10329 Germain DP, Perdu J, Remones V, Jeunemaitre X (2000) Homozygosity for the R1268Q mutation in MRP6, the pseudoxanthoma elasticum gene, is not disease-causing. Login to comment

PMID: 11474653 [PubMed] Germain DP et al: "Pseudoxanthoma elasticum: evidence for the existence of a pseudogene highly homologous to the ABCC6 gene."

No. Sentence Comment

75 Nat Genet 2000;25:228-31. 4 Germain DP, Perdu J, Remones V, Jeunemaitre X. Homozygosity for the R1268Q mutation in MRP6, the pseudoxanthoma elasticum gene, is not disease-causing. Login to comment

PMID: 11536079 [PubMed] Le Saux O et al: "A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum."

No. Sentence Comment

129 Premature termination mutations frequently result in the nonsense-mediated decay (NMD) of mutant mRNA products and significantly reduce mutant transcript levels (Maquat 1996; Nagy and Table 3 Missense Neutral Variants Identified in the ABCC6 Gene in a Cohort of 122 Patients CHANGE IN STATUS a ORIGIN(S)b EXON(S) NO. OF ALLELES/ PXE CHROMOSOMES NO. OF ALLELES/ CONTROL CHROMOSOMES c Amino Acid Nucleotide G61D 182GrA ht SA 2 1/244 0/200 G207R 619GrA ht Belgium 6 1/244 0/200 R265G 793ArG ht Belgium 7 1/244 0/200 K281Ed 841ArG ht, hm SA 8 5/8d Nd I319Vd 955ArG ht, hm SA 8 5/8d Nd N497K 1489CrA ht Belgium 12 1/244 0/200 V614A 1841TrC ht, hm All 14 200/244 163/200 H632Qd 1896CrA ht, hm SA, Belgium 15 17/24d Nd L953H 2858TrA ht US 22 1/244 0/200 W1241C 3723GrC ht Germany 26 1/244 0/200 R1268Q 3803GrA ht All 27 23/244 31/200 a ht p heterozygote; hm p homozygote. Login to comment
156 Most of the neutral variants were unique; however, two of these alleles (V614A and R1268Q) were found at 81.9% and 9.4%, respectively, in the cohort of patients with PXE. Login to comment
312 J Biol Chem 275:13098-13108 Germain DP, Perdu J, Remones V, Jeunemaitre X (2000) Homozygosity for the R1268Q mutation in MRP6, the pseudoxanthoma elasticum gene, is not disease-causing. Login to comment

PMID: 12069597 [PubMed] Cai J et al: "Nucleotide binding and nucleotide hydrolysis properties of the ABC transporter MRP6 (ABCC6)."

No. Sentence Comment

55 Interestingly, most of the single amino acid substitutions mapped in NBD2 of MRP6 (R1114P, R1138Q/ W, R1314W, W1259G, R1268Q) with none in NBD1. Login to comment

PMID: 12384774 [PubMed] Le Saux O et al: "Evidence for a founder effect for pseudoxanthoma elasticum in the Afrikaner population of South Africa."

No. Sentence Comment

89 335 Table 3 Silent and neutral variants identified in the ABCC6 gene in a cohort of 24 South African patients with PXE (hm homozygote, ht heterozygote, aa amino acid changes, nt nucleotide changes, i- the intron in which the variant is located, No. of alleles number of variants found in the 48 PXE chromosomes analysed in this study aVariants identified by sequencing only; variants identified in either or both ABCC6 pseudogenes have not been indicated in this table aa nt Status Exon Origin No. of alleles G61D 182G→A ht 2 Afrikaner 1 T215T 645G→A ht 6 Afrikaner 2 K281Ea 841A→G ht, hm 8 Afrikaner, UK 2 T285Ta 855C→T ht, hm 8 Afrikaner, UK 2 I319Va 955A→G ht, hm 8 Afrikaner, UK 2 N411N 1233T→C ht, hm 10 Afrikaner, UK 20 V415V 1245G→A ht, hm 10 All 20 none IVS11+73G→C ht i-11 Afrikaner, UK 2 none IVS11-45C→A ht i-11 UK 1 none IVS11-41A→G ht, hm i-11 Afrikaner, UK 5 none IVS11-22C→A ht i-11 Afrikaner 1 V614A 1841T→C ht, hm 14 All 16 T630Ta 1890C→G ht, hm 15 Afrikaner, UK 11 H632Qa 1896C→A ht, hm 15 Afrikaner, UK 11 A830A 2490C→T ht, hm 19 Afrikaner, UK 6 none IVS21+30G→A ht i-21 UK 2 P945P 2835C→T ht, hm 22 Indian, UK 3 none IVS22-5delTCCC-8 ht i-22 UK 1 none IVS24-16T→C ht i-24 UK 1 none IVS24-3C→T ht i-24 AFK 1 none IVS25+55T→C ht i-25 Afrikaner, UK 8 none IVS25+90G→A ht, hm i-25 All 21 R1268Q 3803G→A ht, hm 27 Afrikaner, UK 4 none IVS27-6G→A ht i-27 Afrikaner 1 none IVS28+49C→T ht, hm i-28 Afrikaner 18 I1350L 4048A→C ht 29 UK 1 none 3` UTR+17G→A ht 3`UTR Afrikaner 2 Silent and neutral variants of ABCC6 An additional 27 variants, assumed to be neutral or silent, were identified in the course of the ABCC6 screening of our cohort of 24 South African PXE individuals (Table 3). Login to comment
92 Six other variants (G61D, K281E, I319V, V614A, H632Q and R1268Q) resulted in amino acid changes but appeared not to segregate with the disease in PXE pedigrees and were therefore likely to be neutral. Login to comment

PMID: 12586381 [PubMed] Cai J et al: "Overexpression, purification, and functional characterization of ATP-binding cassette transporters in the yeast, Pichia pastoris."

No. Sentence Comment

316 Recently, a rare MRP6 mutation (R1268Q) in a PXE patient was found to be associated with type IV hyperlipidemia and hypoalphalipoproteinemia, suggesting that MRP6 may be a determinant of plasma lipoproteins [141]. Login to comment

PMID: 12673275 [PubMed] Hu X et al: "ABCC6/MRP6 mutations: further insight into the molecular pathology of pseudoxanthoma elasticum."

No. Sentence Comment

159 Table 4 Polymorphic sequence changes identified in ABCC6 Nucleotide Amino acid Location Estimated frequency (%) CA(18) F Intron4 68 V415V 1245G>A 10 33 V614A 1841T>C 14 52 T630T 1890C>G 15 22 H632Q 1896C>A 15 24 A830G 2490C>G 19 25 P945P 2846C>T 22 50 L968L 2904G>A 22 20 Int(22) F Intron22 50 R1268Q 3808G>A 27 38 The definition of disease-associated alleles essentially follows the criteria described by Le Saux et al.22 In summary, sequence variants predicted to result in nonsense or splice-site changes were considered to be disease-associated alleles if they are absent in DNA of a panel of at least 100 controls. Login to comment

PMID: 12714611 [PubMed] Hu X et al: "Analysis of the frequent R1141X mutation in the ABCC6 gene in pseudoxanthoma elasticum."

No. Sentence Comment

104 Three of these were used in this study to construct the following haplotypes: (1) 1896 C3A in exon 15 predicting an H632Q substitution, (2) 2490 C3G in exon 19 predicting an A830G substitution, and (3) 3803 G3A in exon 27 predicting a R1268Q substitution. Login to comment

PMID: 12928920 [PubMed] Morcher M et al: "Heterozygous carriers of Pseudoxanthoma elasticum were not found among patients with cervical artery dissections."

No. Sentence Comment

10 One patient with PXE was compound heterozygous for two missense point mutations, in the second patient with PXE we did not find changes in the ABCC6 gene.We observed several missense mutations (H623Q, R3190W and R1268Q) in the patients with sCAD, but these mutations were not disease specific, since they were also detected in a series of 25 healthy control subjects. Login to comment
35 We found three missense mutations in our patients with sCAD (H623Q, R1064W and R1268Q). Login to comment
45 However, the R1141X muTable ABCC6sequencevariationin12patientswithsCADand2patientswithPXE exon nucleotide Amino-acid Occurrence Occurrence position change among patients among controls 10 1233T¡C synonymous sCAD not tested 10 1245G¡A synonymous sCAD not tested 15 1890C¡G synonymous sCAD not tested 15 1896C¡A H623Q sCAD + 19 2490C¡T synonymous sCAD not tested 20 2631C¡A synonymous sCAD not tested 22 2835C¡T synonymous sCAD not tested 22 2836C¡A L946I PXE - 23 3190C¡T R1064W sCAD + 24 3389C¡T T1130M PXE - 27 3803G¡A R1268Q sCAD + tation is common in European patients, whereas a large deletion of exons 23-26 is repeatedly found in patients from the United States [22]. Login to comment
51 Several missense mutations (H632Q in exon 15, R1064W in exon 23 and R1268Q in exon 27) were found. Login to comment
53 A missense mutation (N411K) at this same nucleotide position was described as disease causing in a patient with PXE [13].The analysis of 25 control subjects revealed that none of the sequence variants found in the group of sCAD patients was specific, as each mutation was also detected among control subjects.Two of the missense mutations (H623Q and R1268Q) had already been found in healthy subjects [13, 18]. Login to comment

PMID: 15235502 [PubMed] Perdu J et al: "[Microvascular involvement in pseudoxanthoma elasticum. Capillaroscopic findings]."

No. Sentence Comment

61 5 Germain DP, Perdu J, Remones V, Jeunemaître X. Homozygosity for the R1268Q Mutation in MRP6, the Pseudoxanthoma Elasticum Gene, Is Not Disease-Causing. Login to comment

PMID: 15459974 [PubMed] Gheduzzi D et al: "ABCC6 mutations in Italian families affected by pseudoxanthoma elasticum (PXE)."

No. Sentence Comment

134 Interestingly, it has been observed that a particular ABCC6/MRP6 polymorphism, called c.3803G>A (p.R1268Q), is associated with reduced amount of plasma triglycerides and higher plasma HDL cholesterol (Wang et al., 2001). Login to comment

PMID: 15723264 [PubMed] Hendig D et al: "New ABCC6 gene mutations in German pseudoxanthoma elasticum patients."

No. Sentence Comment

181 Germain DP, Perdu J, Remones V, Jeunemaitre X (2000) Homozygosity for the R1268Q mutation in MRP6, the pseudoxanthoma elasticum gene, is not disease-causing. Login to comment
134 All but two of the PXE patients who were identified to be heterozygous carriers of the six novel mutations (p.M751K, p.R760W, p.L851P, p.S1403R, and c.2835_ 2850del16) were also found to carry one other PXE-causing ABCC6 mutation (c.2787+1G>T, p.R1141X, c.3736-1G>A, p.R1268Q). Login to comment

PMID: 15760889 [PubMed] Aranyi T et al: "Identification of a DNA methylation-dependent activator sequence in the pseudoxanthoma elasticum gene, ABCC6."

No. Sentence Comment

27 In this line, the association of the R1268Q allele with variations of plasma triglyceride and the high density lipoprotein cholesterol level has been observed (19). Login to comment

PMID: 16086317 [PubMed] Miksch S et al: "Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6."

No. Sentence Comment

209 Type and Frequency of Polymorphisms in ABCC6 Identi'ed in170 Chromosomes of 81 PXE FamiliesÃ Exon/ Intron Nucleotide substitution Amino acid change Location Frequency (] of families) Referencea E 03 c.232G4A p.A78T ABCC6-C2 81 This study, (C,H) IVS 03 c.345112T4C Intron duplication 81 This study IVS 03 c.345126C4T Intron 1 This study IVS 03 c.346À6G4A Intron 10 This study, (C) E 04 c.373G4A p.E125K ABCC6-C1 81 This study, (C) E 04 c.473C4T p.A158V ABCC6-C2 81 This study, (C) IVS 04 c.474113 G4A Intron duplication 2 This study IVS 04 c.474143C4T Intron duplication 80 This study, (C) IVS 04 c.475À76A4C Intron duplication 81 This study IVS 04 c.475À45C4T Intron 3 This study IVS 04 c.475À22T4C Intron duplication 80 This study, (C) E 05 c.549G4A L183L ABCC6 2 This study, (E) IVS 05 c.600123C4T Intron 1 This study E 06 c.645G4A T215T ABCC6 8 This study, (C) IVS 06 c.662112C4T Intron 1 This study, (C) E 07 c.793A4G R265G ABCC6-C1 81 This study, (C,H) IVS 07 c.794136A4C Intron duplication 81 This study, (C) E 08 c.841A4G K281E ABCC6-Cx 81 This study, (H) E 08 c.855C4T T285T ABCC6-C1 81 This study, (C) E 08 c.955A4G I319V ABCC6-Cx 81 This study, (H) E 09 c.1077A4G S359S ABCC6, ABCC6-C1 1 This study, (C,H) E 09 c.1132C4T Q378X ABCC6-C1 81 This study, (C,H) E 09 c.1141T4C L381L ABCC6, ABCC6-C1 81 This study, (C,H) IVS 09 c.117616C4T No SSM Intron 1 This study E 10 c.1233T4C N411N ABCC6 1 This study, (B,L) E 10 c.1245G4A V415V ABCC6 Frequent This study, (B,L) IVS 10 c.133817C4G Intron Frequent This study IVS 10 c.1338120C4G Intron Frequent This study IVS 10 c.1338162G4C Intron Frequent This study IVS 11 c.1432À41A4G Intron Frequent This study, (E) E 12 c.1540G4A V514I ABCC6 1 This study IVS 12 c.1635147C4T Intron Frequent This study E 14 c.1841T4C V614A ABCC6 Frequent This study, (B,E) IVS 14 c.1868À57G4A Intron 3 This study E 15 c.1890C4G T630T ABCC6 Frequent This study, (B,L) E 15 c.1896C4A H632Q ABCC6 Frequent This study, (C,G) E 17 c.2171G4A R724K ABCC6 2 This study E 17 c.2175A4T V725V ABCC6 2 This study E 17 c.2224A4G I742V ABCC6 2 This study E 19 c.2490C4T A830A ABCC6 Frequent This study, (E) E 22 c.2820T4G R940R ABCC6 1 This study E 22 c.2835C4T P945P ABCC6 8 This study, (J) E 22 c.2836C4A L946I ABCC6 3 This study E 22 c.2904G4A L968L ABCC6 1 This study, (J) E 23 c.3190C4T R1064W ABCC6 2 This study IVS 24 c.3507À16T4C No SSM Intron 4 This study IVS 24 c.3507À3C4T No SSM Intron 3 This study E 27 c.3803G4A R1268Q ABCC6 Frequent This study, (C,M) IVS 27 c.3883À24G4A Intron 1 This study IVS 28 c.4041149C4T Intron Frequent This study, (E) IVS 28 c.4042À30C4T Intron Frequent This study IVS 29 c.420819G4A Intron 2 This study E 30 c.4305C4T G1435G ABCC6 1 This study IVS 30 c.4405À31G4A Intron Frequent This study 30 UTR c.4512117G4A UTR 5 This study, (E) 30 UTR c.4512138G4A UTR 1 This study ÃDNA mutation numbering is based on the ABCC6 cDNA sequence (GenBank accession no. AF076622.1) and 11 corresponds to the A of the ATG translation initiation codon of the reference sequence. Login to comment
199 Coding sequence SNPs were considered as neutral (non-disease-causing) when they resulted in a synonymous amino acid substitution or a nonsynonymous substitution that did not cosegregate with the disease haplotype and phenotype (p.V614A, p.R724K, p.I742V, p.L946I, p.R1064W, and p.R1268Q) or did cosegregate with other PXE mutations in linkage disequilibrium in individual families (p.V514I, p.H632Q, and p.R1268Q). Login to comment

PMID: 16086762 [PubMed] Meyer S et al: "Elastosis perforans serpiginosa-like pseudoxanthoma elasticum in a child with severe Moya Moya disease."

No. Sentence Comment

51 These comprise three adjacent amino acid substitutions in exon 27 (Arg1268Gln, Arg1273Lys and Glu1293Lys) and a single Arg1418Gln exchange in exon 30 (Fig. Login to comment
53 The Arg1268Gln substitution, which results from a G fi A nucleotide exchange in position 3803, was found in both the index patient and her healthy father. This substitution has previously been suggested to be causatively linked to PXE,9 but was later recognized as a common polymorphism with significant allelic frequency.10 In contrast, the Arg1273Lys and Glu1293Lys substitutions in exon 27 are new and have not previously been reported. Login to comment

PMID: 16854481 [PubMed] Kiec-Wilk B et al: "Acute myocardial infarction and a new ABCC6 mutation in a 16-year-old boy with pseudoxanthoma elasticum."

No. Sentence Comment

24 The patient was also a heterozygous carrier of a neutral polymorphism (c.3803G>A; R1268Q) in exon 27 [2] (Fig. 3). Login to comment

PMID: 18936737 [PubMed] Hendig D et al: "Gene expression profiling of ABC transporters in dermal fibroblasts of pseudoxanthoma elasticum patients identifies new candidates involved in PXE pathogenesis."

No. Sentence Comment

173 It is mainly involved in HDL biosynthesis and cholesterol efflux.39,40 Polymorphisms in the ABCA1 were associated with cardiovascular disease and low plasma HDL levels.41-43 Wang et al previously reported that plasma HDL concentrations varied in a PXE patient and carriers of the ABCC6/MRP6 polymorphisms p.R1268Q.44 Furthermore, abcc6 knockout mice developed a 25% reduction in plasma HDL cholesterol.8 ABCA3 is a regulator of lamellar body metabolism and was reported to form lipid containing vesicles in human embryonic kidney cells.45 Little is known about the physiological function of the ABCA6-like transporters including ABCA6, ABCA9, ABCA10. Login to comment

PMID: 20491760 [PubMed] Li Q et al: "Mutation analysis (ABCC6) in a family with pseudoxanthoma elasticum: presymptomatic testing with prognostic implications."

No. Sentence Comment

51 7 Germain DP, Perdu J, Remones V, Jeunemaitre X. Homozygosity for the R1268Q mutation in MRP6, the pseudoxanthoma elasticum gene, is not disease-causing. Login to comment
17 The analysis of the ABCC6 gene was performed by polymerase chain reaction amplification of all exons and flanking intronic sequences, followed by automated nucleotide sequencing, as described previously.2 Two homozygous sequence variants were identified in the ABCC6 gene of the proband: p.R1221H and p.R1268Q. Login to comment
22 In contrast, the p.R1268Q sequence variant has been suggested to be a relatively common polymorphism with an allelic frequency of ~30% in healthy Caucasian and Japanese populations.7,8 Collectively, it appears that p.R1221H is the pathogenic mutation resulting in PXE, when present in both alleles, as in the case of the proband of this study. Login to comment
34 The mutation p.R1221H cosegregates in the family with an allelic polymorphism, p.R1268Q (a). Login to comment

PMID: 16835894 [PubMed] Schulz V et al: "Mutational analysis of the ABCC6 gene and the proximal ABCC6 gene promoter in German patients with pseudoxanthoma elasticum (PXE)."

No. Sentence Comment

183 This assumption is confirmed by the fact that an association of the polymorphism p.R1268Q in the exon 27 of the ABCC6 gene with plasma lipoprotein levels has already been observed (Wang et al., 2001). Login to comment

PMID: 19284998 [PubMed] Sato N et al: "Novel mutations of ABCC6 gene in Japanese patients with Angioid streaks."

No. Sentence Comment

84 We identified 8 nonsynonymous variants and a deletion variant in the exon regions; p.R419Q (Exon10), p.S587C (exon13), p.V614A (Exon14), p.H632Q (Exon15), c.2542delG (Exon19), p.A950V (Exon22), p.R1268Q (Exon27) and p.E1427K (Exon30). Login to comment
104 Disease-causing mutations The homozygous p.R419Q and the homozygous p.R1268Q were found in 2 subjects with the homozygous GTGG/GTGG diplotype. The homozygous c.2542delG and the homozygous p.H632Q or homozygous p.V614A were found in each subject with the homozygous ATGA/ATGA diplotype. The homozygous Del_Exon23 was found in 2 subjects with the homozygous GTGA/GTGA diplotype. Login to comment
106 The heterozygous p.E1427K and p.V614A or p.H632Q or p.R1268Q were found in a subject with the heterozygous GTAA/ATGG diplotype. The heterozygous c.2542delG and p.V614A or p.H632Q were found in a subject with the heterozygous GTAA/ACAA diplotype. The heterozygous p.S587C was found in a subject with the heterozygous GTGA/GCGA diplotype, and the heterozygous p.A950V was found in a subject with the heterozygous GTAA/GCAA diplotype. Login to comment
109 Consequently, p.S587C (exon13), p.V614A (Exon14), p.H632Q (Exon15), p.A950V (Exon22) and p.R1268Q (Exon27) were excluded from among the disease-causing mutations because they were seen in the control group. Login to comment
110 Of the 9 variants, p.V614A, p.H632Q and p.R1268Q were previously reported as non-causal variants for PXE. Although c.2542delG (Exon19) was seen in the control group, this is defined as the disease-causing mutation because it yields a premature stop codon. Login to comment
157 Exon Mutation AS Control Decision Wild/Wild Wild/Mut Mut/Mut Wild/Wild Wild/Mut Mut/Mut Undetermine 10 c.1256G>A (p.R419Q) 45 3 6 150 0 0 0 * 10 c.1264G>A (p.E422K) 53 1 0 150 0 0 0 * 10 c.1283A>G (p.N428S) 54 0 0 148 2 0 0 # 10 c.1312G>A (p.V438M) 54 0 0 149 1 0 0 # 13 c.1760C>G (p.S587C) 53 1 0 149 1 0 0 # 14 c.1841T>C (p.V614A) 40 12 2 89 56 5 0 $ 15 c.1896C>A (p.H632Q) 30 15 9 90 55 5 0 $ 19 c.2542delG 34 13 7 149 1 0 0 * 22 c.2849C>T (p.A950V) 53 1 0 149 1 0 0 # 23 Del_Exon23 52 0 2 150 0 0 0 * 27 c.3803G>A (p.R1268Q) 29 16 9 105 42 3 0 $ 27 c.3774-3775insertC 53 1 0 147 0 0 3 * 30 c.4279G>A (p.E1427K) 53 1 0 150 0 0 0 * For ABCC6 proteins, the designations for the mutations refer to the position of the amino acid substitution, where amino acid terminus. Nonsynonymous variants were shown by the amino acid numbers started by the strat codon methionine. The cDNA base numbers refer to the nucleotide in the cDNA, where nucleotide 1 is the A of the first ATG. * Causal mutation definitely. Login to comment

PMID: 21671388 [PubMed] Uitto J et al: "Pseudoxanthoma elasticum: progress in diagnostics and research towards treatment : Summary of the 2010 PXE International Research Meeting."

No. Sentence Comment

25 There are recent suggestions, however, that certain mutations in ABCC6 may bestatistically associatedwithinvolvementofspecifictargetorgans, such as the p.R1268Q mutation being associated with early onset of angioidstreaks[Satoetal.,2009;Lietal.,2011a],andthestopcodon mutation p.R1141X possibly predisposing the individuals to car- diovascularinvolvementindependentofhyperlipidemiainpatients with PXE [K€obl€os et al., 2010; Pisciotta et al., 2010]. Login to comment

PMID: 20103563 [PubMed] Klaassen CD et al: "Xenobiotic, bile acid, and cholesterol transporters: function and regulation."

No. Sentence Comment

7172 These findings are consistent with the R1268Q variant of ABCC6 in pseudoxanthoma elasticum patients that is associated with type IV hyperlipoproteinemia with hypoalphalipoproteinemia (Wang et al., 2001a). Login to comment
7169 These findings are consistent with the R1268Q variant of ABCC6 in pseudoxanthoma elasticum patients that is associated with type IV hyperlipoproteinemia with hypoalphalipoproteinemia (Wang et al., 2001a). Login to comment

PMID: 20799350 [PubMed] Kelly L et al: "Functional hot spots in human ATP-binding cassette transporter nucleotide binding domains."

No. Sentence Comment

72 Predictions of the Functional Effects of 40 nsSNPs in ABC Transporters Comon name HUGO name Mutation NBD Prediction BSEP ABCB11 E592Q NBD1 Neutral BSEP ABCB11 N591S NBD1 Neutral BSEP ABCB11 Q558H NBD1 Neutral BSEP ABCB11 V444A NBD1 Neutral BSEP ABCB11 E1186K NBD2 Disease MDR1 ABCB1 P1051A NBD2 Neutral MDR1 ABCB1 S1141T NBD2 Neutral MDR1 ABCB1 T1256K NBD2 Disease MDR1 ABCB1 V1251I NBD2 Neutral MDR1 ABCB1 W1108R NBD2 Disease MRP2 ABCC2 I670T NBD1 Disease MRP2 ABCC2 L849R NBD1 Disease MRP2 ABCC2 C1515Y NBD2 Disease MRP3 ABCC3 D770N NBD1 Neutral MRP3 ABCC3 K718M NBD1 Neutral MRP3 ABCC3 T809M NBD1 Disease MRP3 ABCC3 V765L NBD1 Disease MRP3 ABCC3 Q1365R NBD2 Disease MRP3 ABCC3 R1297H NBD2 Disease MRP3 ABCC3 R1348C NBD2 Disease MRP3 ABCC3 R1381S NBD2 Disease MRP4 ABCC4 G487E NBD1 Disease MRP4 ABCC4 K498E NBD1 Neutral MRP4 ABCC4 R1220Q NBD2 Neutral MRP4 ABCC4 T1142M NBD2 Neutral MRP4 ABCC4 V1071I NBD2 Neutral MRP6 ABCC6 I1330L NBD1 Neutral MRP6 ABCC6 I742V NBD1 Neutral MRP6 ABCC6 P664S NBD1 Neutral MRP6 ABCC6 R724K NBD1 Neutral MRP6 ABCC6 R769K NBD1 Neutral MRP6 ABCC6 A1291T NBD2 Neutral MRP6 ABCC6 E1369K NBD2 Neutral MRP6 ABCC6 G1327E NBD2 Disease MRP6 ABCC6 L1416R NBD2 Disease MRP6 ABCC6 R1268Q NBD2 Disease MRP6 ABCC6 R1461H NBD2 Disease MXR ABCG2 I206L NBD1 Neutral MXR ABCG2 P269S NBD1 Disease MXR ABCG2 Q141K NBD1 Neutral nsSNPs. Login to comment

PMID: 23408347 [PubMed] Leftheriotis G et al: "The vascular phenotype in Pseudoxanthoma elasticum and related disorders: contribution of a genetic disease to the understanding of vascular calcification."

No. Sentence Comment

109 Althoughseveralmissense mutations (H623Q, R3190W, and R1268Q) were found in the patients with carotid dissection, these mutations were not disease-causing as they were also detected in healthy subjects (Morcher et al., 2003). Login to comment

PMID: 23674961 [PubMed] Mizutani Y et al: "ABCC6 Mutation in Patients with Angioid Streaks."

No. Sentence Comment

8 The base substitution of G3803A was identified in exon 27, with a change in the amino acid from CGG to CAG (R1268Q). Login to comment
11 Highly significant differences were observed in both genotype and allele frequencies of R1268Q between patients with AS and control subjects (p<0.001, p<0.002; chi-square test). Login to comment
12 In conclusion, the missense mutation R1268Q in the ABCC6 gene is not a specific marker of PXE, but is associated with the disease state of AS. Login to comment
72 This substitution yields an amino acid change from CGG (Arg) to CAG (Gln) (R1268Q) (Fig. 2). Login to comment
73 We investigated the frequencies of the G3803A (R1268Q) genotypes by the RFLP method (Fig. 3). Login to comment
77 Arrow indicates the nucleotide constitution with a change in the amino acid (R1268Q). Login to comment
104 This nucleotide substitution results in a substitution of the amino acid arginine (CGG) to glutamine (CAG) (R1268Q). Login to comment
105 The association of R1268Q with PXE has been reported, but opinions regarding this relationship remain controversial. Login to comment
106 Ringpfeil et al (10) reported that R1268Q was not found in control subjects, and concluded that it represented a mutation and not a polymorphism in patients with PXE. Login to comment
108 On the other hand, other studies have reported that R1268Q was a polymorphism, and not a mutation (20, 21). Login to comment
110 Germain et al (22) determined the frequency of R1268Q in 62 healthy Caucasian volunteers, and reported the genotype frequencies in their control subjects as G/G 66%, G/A 29% and A/A 5%. Login to comment
111 They detected no differences in genotype frequency between the control subjects and patients with PXE, and concluded that R1268Q was a harmless polymorphism. Login to comment
112 The genotype frequency of R1268Q in Caucasians is very similar to that in healthy Japanese in the present study (Table 2). Login to comment
113 There was no significant difference in genotype frequency between our Japanese controls and the reported Caucasian volunteers (p=0.50), suggesting that there is no racial difference in the frequency of R1268Q. Login to comment
121 In the present study, we found significant differences both in genotype frequency and allele frequency of R1268Q between patients with AS and the controls. Login to comment
123 These results suggest that R1268Q may represent a genetic marker for AS rather than PXE. Login to comment
124 Germain et al (22) described R1268Q as a nonfunctional substitution in case control studies of patients with PXE. Login to comment
125 However, R1268Q seems to have etiological significance in patients with AS in the present study. Login to comment
126 Therefore, detection of R1268Q warrants not only examination for the skin disease PXE, but also investigations of other systemic symptoms including AS and cardiovascular system involvement. Login to comment
137 A single nucleotide substitution was found in exon 27, which resulted in the substitution of an amino acid (R1268Q). Login to comment
138 Significant differences in genotype and allele frequencies of R1268Q were observed between patients with AS and control subjects. Login to comment
139 However, no significant difference in allele frequency of R1268Q was found between patients with AS with and without PXE. Login to comment
140 These findings indicate that R1268Q is not a specific marker of PXE, but is a missense mutation associated with the disease state of AS. Login to comment

PMID: 23802012 [PubMed] Hendig D et al: "New insights into the pathogenesis of pseudoxanthoma elasticum and related soft tissue calcification disorders by identifying genetic interactions and modifiers."

No. Sentence Comment

115 Wang et al. (2001) reported an association of the frequent ABCC6 p.R1268Q variant (c.3803G>A, rs2238472) with plasma triglyceride and low HDL (high-density lipoprotein) cholesterol. Login to comment