ABCMdb

ABCC6 p.Gln378*

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Publications

PMID: 18220559 [PubMed] Yu XQ et al: "Multidrug resistance associated proteins as determining factors of pharmacokinetics and pharmacodynamics of drugs."

No. Sentence Comment

406 MRP Chromosomal location Amino acid variation Nucleotide variation Location References Lys13Asn G39GC Exon1 His68Tyr C202T Exon2 Ser346Phe C1037T Exon9 Gln513Lys C1537A Exon12 Arg1297His G3890A Exon27 MRP3 17q21.3 Gly1423Arg G4267A Exon29 [241] MRP4 13q32.1 Unknown MRP5 3q27 Unknown L63L W64R 189G>C 190T>C Exon2 Exon2 [250] T364R Q378X 1091C>G 1132C>T Exon9 Exon9 [260, 261] R518X R518Q 1552 C>T 1553G>A Exon12 Exon12 [247, 262] R1141X R1138Q T1130M R1114C M1127T 3421C>T 3413G>A 3389C>T 3340C>T 3380C>T Exon24 Exon24 Exon24 Exon24 Exon24 [246, 247] R1275X 3823C>T Exon27 [246] P1346S 4036C>T Exon28 [246] MRP6 16p13.1 E1400K 4198G>A Exon29 [247] MRP7 6p12-21 Unknown MRP8 16q12.1 Unknown MRP9 16q12.1 Unknown CONCLUSIONS AND FUTURE DIRECTIONS MRPs which belong to the ABC transporter family are able to transport a remarkable array of diverse endo- and xenobiotics and their metabolites. 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

24 This nucleotide substitution alters the codon (CAG) for glutamine to a stop codon (TAG), predicting termination of translation at position 378 of the ABCC6 protein (Q378X). Login to comment
26 Mutation Q378X predicted the loss of a PstI Figure 1 Detection of a frameshift mutation (c196insT) in what was initially thought to be exon 2 of the ABCC6 gene. Login to comment
32 Figure 2 Detection of a nonsense mutation (Q378X) in what was initially thought to be exon 9 of the ABCC6 gene. Login to comment
36 (B) Lower panel: mutation c1132C>T (Q378X) predicted the loss of a PstI restriction site. Login to comment
38 Five healthy volunteers, who although unaVected with PXE display heterozygozity for the Q378X nonsense mutation, are shown. Login to comment
42 To test for the presence or absence of this nucleotide change, we used PstI to digest PCR amplified genomic DNA of 79 additional controls and found all of them to be heterozygotes for the Q378X nonsense mutation (fig 2). Login to comment
99 + We have characterised two truncating mutations (c196insT and Q378X) in the ABCC6 gene, always found in the heterozygous state, not only in PXE patients but also in all controls. Login to comment

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

No. Sentence Comment

180 Indeed, a nucleotide substitution in exon 9-that would result in a nonsense mutation Q378X (1132CrT)-and a single insertion in exon 2 (196-197insT) were observed in all Afrikaner and several European patients who had already been shown to be homozygous or compound heterozygous for other ABCC6 mutations. Login to comment
183 Mutations 196-197insT and Q378X were found to be randomly associated with all of the homozygous or compound heterozygous mutant alleles. Login to comment
184 Because these mutations would lead to premature termination of translation, both Q378X and 196-197insT were potentially disease-causing alleles. Login to comment
195 The sequence divergence between these putative pseudogenes and ABCC6 (absent in any published ABCC6 mRNA sequences) corresponded to several nucleotide substitutions and insertions that we have detected in our cohort of patients with PXE, including Q378X and 196-197insT (table 4). Login to comment
207 Moreover, the NCBI map of chromosome 16 currently reports at least nine gaps of unknown length between ABCC6 and the putative pseudogene contain- Table 4 Nucleotide and Apparent Amino Acid Changes Found in Two ABCC6 Pseudogenes CHANGE IN EXONAmino Acid Nucleotide V39Va 117ArG 2 L63La 189GrC 2 W64Qa 190TrC/191GrA 2 … 196-197insT 2 A78T 232GrA 3 A158V 473CrT 4 S359S 1077ArG 9 Q378X 1132CrT 9 L381L 1141TrC 9 a Variants found in homozygous states. Login to comment

PMID: 11702217 [PubMed] Pulkkinen L et al: "Identification of ABCC6 pseudogenes on human chromosome 16p: implications for mutation detection in pseudoxanthoma elasticum."

No. Sentence Comment

45 One of the variants, 1132C→T, resulted in a STOP codon at amino 357 acid position 378 (a mutation designated as Q378X; Fig.1B). Login to comment
52 Sequence analysis of the PCR products spanning exon 9 revealed three nucleotide changes, among which 1132C→T results in the substitution of a glutamine residue by a termination codon (Q378X). Login to comment
54 The presence of Q378X in exon 9 was verified in 18 PXE patients (C) and in normal controls (not shown) by PstI restriction enzyme digestion, which resulted in an undigested fragment of 266 bp in all samples studied, thereby reflecting the presence of the allele containing the Q378X mutation. Login to comment
59 They also contain stop-codon-causing mutations 196insT in exon 2 and Q378X in exon 9. 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

38 Table 2 Summary of ABCC6/MRP6 mutations associated with PXE known today: our data combined with those of the literature Mutation Protein alteration Nucleotide substitution Location Reference Nonsense Q378X 1132C > T Exon 9 19,20 R518X 1552C > T Exon 2 41 Q749X 2247C > T Exon 17 This study Y768X 2304C > A Exon 18 22 R1030X 3088C > T Exon 23 22 R1141X 3421C > T Exon 24 12,20,22,38,39, this study R1164X 3490C > T Exon 24 12,41 Q1237X 3709C > T Exon 26 22 R1398X 4192C >T Exon 29 22 T364R Missense N411K 1091C > G Exon 9 20 A455P 1233T > G Exon 10 22 R518Q 1363G > C Exon 11 38 F568S 1553G > A Exon 12 22,38 L673P 1703T > C Exon 13 22 R765Q 2018T > C Exon 16 22 R1114P 2294G > A Exon 18 22, this study R1114H 3341G > C Exon 24 22 S1121W 3341G > A Exon 24 This study T1130M 3362C > G Exon 24 22 R1138W 3390C > T Exon 24 This study R1138Q 3412C > T Exon 24 12 R1138P 3413G > A Exon 24 12,22 G1203D 3413G > C Exon 24 22 R1221C 3608G > A Exon 25 22 V1298F 3663C > T Exon 26 This study T1301I 3892G > T Exon 28 22 G1302R 3902C > T Exon 28 22 A1303P 3904G > A Exon 28 22, this study R1314W 3907G > C Exon 28 22, this study R1314Q 3940C > T Exon 28 22 G1321S 3941G > A Exon 28 22 R1339C 3961G > A Exon 28 22 Q1347H 4015C > T Exon 28 22,39 G1354R 4041G > C Exon 28 22 D1361N 4060G > C Exon 29 20,38 K1394N 4081G > A Exon 29 22 I1424T 4182G > T Exon 29 This study R1459C 4271T > C Exon 30 22 4377C > T Exon 30 This study Frameshift IVS17-12delT T Intron 17 This study IVS21+1G>T Intron 21 22,38 IVS26-1G>A Intron 26 12,21,22 179del 9 Exon 2 20 179-195del Exon 2 22 960del C Exon 8 41 1944del22 Exon 16 This study 1995delG Exon 16 22 2322delC Exon 18 22 2542delG Exon 19 41 3775delT Exon 27 This study 4104delC Exon 29 22 4182delG Exon 29 This study 938-939insT Exon 8 22 4220insAGAA Exon 30 This study Large deletion Exons 23-29 21, This study Exon 15 22 ABCC1, ABCC6 41, this study Mutation types The mutation types found in this study are summarized in Table 1. Login to comment

PMID: 12850230 [PubMed] Hu X et al: "Pseudoxanthoma elasticum: a clinical, histopathological, and molecular update."

No. Sentence Comment

193 TABLE 3 Summary of ABCC6 Mutations in PXE Patients Mutation Protein Alteration Nucleotide Substitution Location Reference Nonsense Q378X 1132C Ͼ T Exon 9 16,107 R518X 1552C Ͼ T Exon 12 88 Y768X 2304C Ͼ A Exon 18 67 R1030X 3088C Ͼ T Exon 23 67 R1141X 3421C Ͼ T Exon 24 12,45,67,107,111,112,133 R1164X 3490C Ͼ T Exon 24 88,112 Q1237X 3709C Ͼ T Exon 26 67 R1398X 4192C Ͼ T Exon 29 67 Missense T364R 1091C Ͼ G Exon 9 107 N411K 1233T Ͼ G Exon 10 67 A455P 1363G Ͼ C Exon 11 142 R518Q 1553G Ͼ A Exon 12 67,142 F568S 1703T Ͼ C Exon 13 67 L673P 2018T Ͼ C Exon 16 67 R765Q 2294G Ͼ A Exon 18 67 R1114P 3341G Ͼ C Exon 24 67 S1121W 3362C Ͼ G Exon 24 67 R1138W 3412C Ͼ T Exon 24 111 R1138Q 3413G Ͼ A Exon 24 67,111 R1138P 3413G Ͼ C Exon 24 67 G1203D 3608G Ͼ A Exon 25 67 V1298F 3892G Ͼ T Exon 28 67 T13011 3902C Ͼ T Exon 28 67 G1302R 3904G Ͼ A Exon 28 67 A1303P 3907G Ͼ C Exon 28 67 R1314W 3940C Ͼ T Exon 28 67 R1314Q 3941G Ͼ A Exon 28 67 G1321S 3961G Ͼ A Exon 28 67 R1339C 4015C Ͼ T Exon 28 67,133 Q1347H 4041G Ͼ C Exon 28 67 G1354R 4060G Ͼ C Exon 29 107,142 D1361N 4081G Ͼ A Exon 29 67 11424T 4271T Ͼ C Exon 30 67 Frameshift Splicing IVS21 ϩ 1G ϾT Intron 21 67,142 IVS26-1G ϾA Intron 26 67,111,112 Deletion 179del9 Exon 2 107 179-195del Exon 2 67 960delC Exon 8 88 1944del22 Exon 16 12 1995delG Exon 16 67 2322delC Exon 18 67 2542delG Exon 19 67 3775delT Exon 27 12,67 4101delC Exon 29 67 Insertion 938-939insT Exon 8 67 4220insAGAA Exon 30 12 Intragenic deletion Exon 23-29 67,112 Exon 15 67 Intergenic deletion ABCC6 12,88 LOCAL RETINAL TRANSPORT FUNCTION OF ABCC6 ABCC6 Expression in the Retina Bergen et al detected ABCC6 expression in various tissues in man.12 Low expression levels of ABCC6 were observed in the retina as well as other tissues usually affected by PXE, including skin and vessel wall. 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

68 Cai L, Lumsden A, Guenther UP, Neldner SA, Zach S, Knoblauch H, Ramesar R, Hohl D, Callen DF, Neldner KH, Lindpaintner K, Richards RI, Struk B (2001) A novel Q378X mutation exists in the transmembrane transporter protein ABCC6 and its pseudogene: implications for mutation analysis in pseudoxanthoma elasticum. Login to comment

PMID: 15086542 [PubMed] Chassaing N et al: "Novel ABCC6 mutations in pseudoxanthoma elasticum."

No. Sentence Comment

120 Biochemistry 41:8058-8067, 2002 Cai L, Lumsden A, Guenther UP, et al: A novel Q378X mutation exists in the transmembrane transporter protein ABCC6 and its pseudogene: Implications for mutation analysis in pseudoxanthoma elasticum. J Mol Med 79:536-546, 2001 Cai L, Struk B, Adams MD, et al: A 500-kb region on chromosome 16p13.1 contains the pseudoxanthoma elasticum locus: High-resolution mapping and genomic structure. Login to comment

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

No. Sentence Comment

64 PXE-causative Mutations Recognized (on one and both alleles) in Italian Patients Family/ Proband Affected subjects Age / gender Clinical score Tot Mutations* Allele 1 Allele 2 Mutation type 001 32 F S2,E2 4 p.R518Q p.T1130MI-3097 002 36 M S3,E2,V2,C2 9 p.R518Q p.T1130M I-3013 001 46 F S1,E3 4 p.R1339C None found I-3094 001 57 F S2,E2 4 p.C440G p.P1346S I-3103 001 57 M E2 2 p.V810M p.R1114C I-3076 001 57 F S2,E4,V3 9 p.R1339C p.R1339C I-3016 001 69 F S3,E2,V2 7 p.N411K p.R1138Q missense I-3082 001 23 M S1,E2 3 p.R518Q p.R1141X I-3074 001 27 F S2,E2 4 p.T364R p.R518X I-3015 001 27 F S2,E3 5 p.Q378X p.R600G I-3062 001 45 M S2,E4,V2 8 p.R1141X p.E1400K 001 50 F S1 1 p.R1275X p.E1400K 002 60 F S3,E3 6 p.R1275X p.E1400K I-3067 003 66 F S2,E2 4 p.R1275X p.E1400K 001 61 F S3,E2 4 p.R518Q p.R1141XI-3027 002 63 F S3,E4,V3 10 p.R518Q p.R1141X missense + nonsense 001 23 F S3,E2 5 p.R1141X p.R1141XI-3056** 002 32 M S2,E2 4 p.R1141X p.R1141X 001 27 F S1,E2 3 p.R1141X p.R1141XI-3057** 002 31 M S3,E2 5 p.R1141X p.R1141X 001 28 M S1,E2 3 p.R1141X None foundI-3045 002 32 F S3,E2,V1 6 p.R1141X None found I-3107 001 29 M S2,E1 3 p.R1030X p.R1141X I-3073 001 31 F S3,E2 5 p.R1141X p.R1141X I-3111 001 32 F S1,E2 3 p.R1141X p.R1141X I-3090 001 34 F S2,E1 3 p.R1141X p.R1141X I-3001 001 37 F S3,E2,V2 7 p.R1030X None found 001 40 F S2,E2 4 p.R1141X p.R1141XI-3007** 002 48 F S1,E2 3 p.R1141X p.R1141X I-3114 001 40 M S2,E2,V3,C1,G2 10 p.R518X p.R518X I-3054 001 44 F S2,E3 5 p.R518X p.R518X 001 47 F S3,E4,C2,G1 10 p.R1141X p.R1141XI-3055** 002 50 F S3,E3 6 p.R1141X p.R1141X 001 50 F S3,E4,V3,C2 12 p.R518X p.R1030X 002 52 F S3,E4,V3 10 p.R518X p.R1030X I-3017 003 55 F S3,E2 5 p.R518X p.R1030X I-3100 001 52 M S3,E3 6 p.Q378X p.Q378X I-3051 001 53 F S3,E4,V2 9 p.R1141X p.R1141X I-3034 001 53 M S3,E4,V3 10 p.R1141X p.R1141X I-3093 001 57 F S3,E3,V2,C3 11 p.R518X None found I-3087 001 57 F S3,E4,V2,C2 11 p.Q378X p.Q378X I-3040 001 60 F S3,E4,V2 9 p.R1141X None found I-3033 001 62 F S3,E4 7 p.R1141X p.R1141X nonsense I-3026 001 36 F S3,E2,G1 6 p.R518X c.2248-2_2248- 1del I-3024 001 40 F S1,E2,V3 6 p.R518X p.L1182PfsX96 I-3072 001 41 F S2,E2,C2 6 p.M1127T c.3736-1G>A I-3002 001 50 F S3,E2 5 p.A820P c.3736-1G>A others Family/ Proband Affected subjects Age / gender Clinical score Tot Mutations* Allele 1 Allele 2 Mutation type 002 57 F S2,E4 6 p.A820P c.3736-1G>A I-3008 001 53 F S2,E2,C1 5 p.M1440CfsX24 p.M1440CfsX24 Patients are identified by an international code: I = Italian, 3001 = family number (European patients are numerated from 3000), 001 = subject number. Login to comment
72 ABCC6/MRP6 Mutations Found in Italian PXE Patients Number of families INTRON EXON cDNA* PROTEIN* References 1 9 c.1091C>G p.T364R Pulkkinen et al., 2001 3 9 c.1132C>T p.Q378X Pulkkinen et al., 2001; Cai et al., 2001 1 10 c.1318T>G p.C440G Present study 1 10 c.1233T>G p.N411K Le Saux et al., 2001 7 12 c.1552C>T p.R518X Meloni et al., 2001; Chassaing et al., 2004 3 12 c.1553G>A p.R518Q Le Saux et al., 2001; Chassaing et al., 2004 1 14 c.1798C>T p.R600G Present study 1 17 c.2248-2_2248- 1del - Present study 1 19 c.2428G>A p.V810M Present study 1 19 c.2458G>C p.A820P Present study 3 23 c.3088C>T p.R1030X Le Saux et al., 2001 1 24 c.3340C>T p.R1114C Present study 1 24 c.3380C>T p.M1127T Present study 1 24 c.3389C>T p.T1130M Chassaing et al., 2004; Gotting et al., 2004 1 24 c.3413G>A p.R1138Q Le Saux et al., 2000; Ringpfeil et al., 2000; Le Saux et al., 2001 13 24 c.3421C>T p.R1141X Bergen et al., 2000; Germain et al., 2000; Ringpfeil et al., 2000; Le Saux et al., 2001; Pulkkinen et al., 2001; Uitto et al., 2001; Hu et al., 2003 ; Gotting et al., 2004 1 25 c.3544_3544dupC p.L1182PfsX96 Present study 2 26 c.3736-1G>A - Ringpfeil et al., 2000; Le Saux et al., 2001 1 27 c.3823C>T p.R1275X Present study 2 28 c.4015C>T p.R1339C Le Saux et al., 2001 1 28 c.4036C>T p.P1346S Present study 2 29 c.4198G>A p.E1400K Chassaing et al., 2004 1 30 c.4318_4318delA p.M1440CfsX24 Present study The number of families in which a specific mutation was found (in heterozygous and in homozygous state) is reported. Login to comment
79 In exon 9, c.1132C>T (p.Q378X) mutation was found in homozygosity in two families and in compound heterozygous in one family. Login to comment
81 In order to identify a possible founder origin of recurrent disease-associated alleles, a limited haplotype analysis was performed in 11 unrelated families carrying the same mutation (p.Q378X, p.R518X, p.R1141X) in homozygous state (data not shown). Login to comment
82 The analysis of the two families with the p.Q378X mutation revealed different alleles, identical-by-state. Login to comment
118 Some were recurrent mutations (p.Q378X, p.R518X, p.R518Q, p.R1141X), however the majority of mutations were sporadic variants. Login to comment

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

No. Sentence Comment

180 Cai L, Lumsden A, Guenther UP, Neldner SA, Zäch S, Knoblauch H, Ramesar R, Hohl D, Callen DF, Neldner KH, Lindpaintner K, Richards RI, Struk B (2001) A novel Q378X mutation exists in the transmembrane transporter protein ABCC6 and its pseudogene: implications for mutation analysis in pseudoxanthoma elasticum. J Mol Med 79:536-546 17. Login to comment

PMID: 15894595 [PubMed] Chassaing N et al: "Pseudoxanthoma elasticum: a clinical, pathophysiological and genetic update including 11 novel ABCC6 mutations."

No. Sentence Comment

378 Interestingly, among the 49 different missense mutations in ABCC6 (42 previously published and seven new ones in the present study), the majority (43) replace critical amino acids in intracellular domains (seven and 19 mutations are located in I1424T R1459C 4220insAGAA 4318delA G1354R D1361N K1394N E1400K R1298X 410delC 418delG 3775delT R1275X R1221C D1238H W1223X Q1237X IVS26-1G→A R1114C R1114H R1114P S1121W M1127T T1130M R1138P R1138Q R1138W R1141X R1164X R765Q A766D Y768X A781V 2322delC IVS19-2delAG T364R R391G Q378X Q363_R373del 938_939insT 960delC IVS8+2delTG G199X Y227X 179_195del 179_187del G226R V74del Q749X IVS17-12delTT IVS14-5T→G IVS13-29T→A R600G V1298F G1299S T1301I G1302R A1303P S1307P R1314Q R1314W G1321S L1335P R1339C P1346S Q1347H R1030X F1048del R807Q V810M A820P 254delG L673P 1944_1966del 1995delG R518Q R518X K502M A455P G992R IVS21+1G→T G1203DF568SN411K C440G IVS25-3C→A 3544dupC Ex23_29del 30 Ex15del ABCC6del 252015105 Figure 10 Position of the mutations in the ABCC6 gene. Login to comment
379 Table 2 ABCC6 mutations Nucleotide variation Protein alteration Location (gene ) Location (protein) Reference Missense 676 GRA G226R Exon 7 CL 3 This study 1091 CRG T364R Exon 9 TS 7 63, 78 1171 ARG R391G Exon 9 CL 4 88 1233 TRG N411K Exon 10 CL 4 63, 90 1318 TRG C440G Exon 10 TS 8 63 1363 GRC A455P Exon 11 TS 9 86 1505 ART K502M Exon 12 CL 5 This study 1553 GRA R518Q Exon 12 CL 5 63, 86, 88, 90 1703 TRC F568S Exon 13 ECL 5 90 1798 CRT R600G Exon 14 CL 6 63 2018 TRC L673P Exon 16 NBF 1 90 2294 GRA R765Q Exon 18 NBF 1 87, 90 2297 CRA A766D Exon 18 NBF 1 88 2342 CRT A781V Exon 18 NBF 1 This study 2420 GRA R807Q Exon 19 NBF 1 This study 2428 GRA V810M Exon 19 NBF1 63 2458 GRC A820P Exon 19 NBF1 63 2965 GRC G992R Exon 22 ECL 6 This study 3340 CRT R1114C Exon 24 CL 8 63 3341 GRA R1114H Exon 24 CL 8 87 3341 GRC R1114P Exon 24 CL 8 90 3362 CRG S1121W Exon 24 CL 8 90 3380 CRT M1127T Exon 24 CL 8 63 3389 CRT T1130M Exon 24 CL 8 63, 87, 88 3412 CRT R1138W Exon 24 CL 8 17 3413 GRC R1138P Exon 24 CL 8 90 3413 GRA R1138Q Exon 24 CL 8 17, 63, 88, 90 3608 GRA G1203D Exon 25 TS17 90 3663 CRT R1221C Exon 26 COOH 87 3712 GRC D1238H Exon 26 COOH 88 3892 GRT V1298F Exon 28 NBF 2 90 3895 GRA G1299S Exon 28 NBF 2 This study 3902 CRT T1301I Exon 28 NBF 2 90 3904 GRA G1302R Exon 28 NBF 2 87, 90 3907 GRC A1303P Exon 28 NBF 2 87, 90 3919 TRC S1307P Exon 28 NBF 2 This study 3940 CRT R1314W Exon 28 NBF 2 90 3941 GRA R1314Q Exon 28 NBF 2 90 3961 GRA G1321S Exon 28 NBF 2 90 4004 TRC L1335P Exon 28 NBF 2 88 4015 CRT R1339C Exon 28 NBF 2 18, 63, 90 4036 CRT P1346S Exon 28 NBF 2 63 4041 GRC Q1347H Exon 28 NBF 2 90 4060 GRC G1354R Exon 29 NBF 2 78, 86 4081 GRA D1361N Exon 29 NBF 2 90 4182 GRT K1394N Exon 29 NBF 2 87 4198 GRA E1400K Exon 29 NBF 2 63, 88 4271 TRC I1424T Exon 30 NBF 2 90 4377 CRT R1459C Exon 30 NBF 2 87 Nonsense 595 CRT G199X Exon 5 89 681 CRG Y227X Exon 7 84 1132 CRT Q378X Exon 9 63, 78, 83 1552 CRT R518X Exon 12 63, 84, 88 2245 CRT Q749X Exon 17 87 2304 CRA Y768X Exon 18 90 3088 CRT R1030X Exon 23 63, 90 3421 CRT R1141X Exon 24 15, 17, 18, 63, 78, 85, 87, 88, 90 3490 CRT R1164X Exon 24 84, 85, 88 3668 GRA W1223X Exon 26 88 3709 CRT Q1237X Exon 26 90 3823 CRT R1275X Exon 27 63 4192 CRT R1398X Exon 29 90 Splicing alteration IVS8+2delTG Intron 8 This study IVS13-29 TRA Intron 13 This study IVS14-5 TRG Intron 14 This study IVS17-12delTT Intron 17 87 IVS18-2delAG Intron 17 63 IVS21+1 GRT Intron 21 86, 90 IVS25-3 CRA Intron 25 88 IVS26-1 GRA Intron 26 17, 63, 90 Insertion 938_939insT Frameshift Exon 8 90 3544dupC Frameshift Exon 25 63 4220insAGAA Frameshift Exon 30 15, 87 Small deletion 179_187del Frameshift Exon 2 78 179_195del Frameshift Exon 2 90 Pseudoxanthoma elasticum www.jmedgenet.com NBF1 and NBF2, respectively), four are located in transmembrane domains, and only two mutations have been identified in extracellular domains. Login to comment
385 A common founder effect was identified for mutation R1141X in French and Italian populations.63 88 We found that arginine codon 518 was a recurrently mutated amino acid in a cohort of 19 French families with PXE (11.5% of the detected mutations for each variant R518Q and R518X).88 These two mutations represent 19% of the mutations detected in the Italian population.63 In Japanese patients, neither R1141X nor Ex23_29del mutations were identified, whereas mutations 2542delG and Q378X account for 53% and 25%, respectively.93 In South African families of Afrikaaners, mutation R1339C represents more than half the mutations detected,28 with a common haplotype indicating a founder effect.27 28 These mutations are rarely identified in American or European populations.90 The detection rate in different studies varies from 0.55 to 0.83.63 87 88 90 Lack of mutation detection in some patients could reflect exonic deletions (for example, deletion of exon 15), splice site mutations distant from the coding sequence, mutations in the gene regulatory sequences, or investigation of patients with acquired PXE-like syndrome not related to ABCC6 mutations, such as seen in b thalassaemia and sickling syndromes (see below).94 95 Locus heterogeneity of PXE is unlikely, but cannot currently be ruled out. 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
151 In our initial mutation screen we identified the c.1132C4T (p.Q378X) base change in a consanguineous U.S. family originating from Italy. Login to comment
154 However, in six p.Q378X alleles we identified four distinct haplotypes, suggesting independent recurrence of this mutation. Login to comment
157 Search for MutationsWithin the Duplicated Region (50 UTR, exons 1^ 9) of ABCC6 In the first round of mutation screening (see Materials and Methods, and Supplementary Table S5), sequencing of the PCR products and comparative analysis of the sequencing reads revealed frequent polymorphisms and potential mutations (p.A78T, p.E125K, p.A158V, p.R265G, p.K281E, and p.I319V p.Q378X) (see Tables 1 and 2) that appeared in all families and initially did not cosegregate with familial haplotypes, which suggests that they are likely pseudogene polymorphisms. Login to comment
213 It also provides an explanation as to why the p.Q378X mutation could not be identified as a PXE-causing mutation [Pulkkinen et al., 2001] when an allele-specific PCR approach was applied that excluded the known pseudogenes from amplification, but not the unknown pseudogenes (in contrast to a long-range PCR approach from sequence points outside the duplication region that excludes both known and uncharacterized pseudogenes from amplification). Login to comment
246 PXE Mutations While most mutations are unique variants that represent the typical allelic heterogeneity of a recessive disease, we observed five mutations (p.R1141X [26%], p.I1000_S1403delW1404fsX1463 [11%], p.R1164X [5.3%], p.Q378X [3.5%], and c.278711G4T [3%]) at higher frequencies that accounted for almost 50% (exactly 48.8%) of the PXE mutations. Login to comment
266 Similarly to p.R1164X, the six chromosomes that carry the p.Q378X mutation represent four independent haplotypes. Login to comment

PMID: 17544787 [PubMed] Querques G et al: "Fundus autofluorescence."

No. Sentence Comment

8 We performed a complete ophthalmologic examination, including fundus autofluorescence and optical coherence tomography (Fig 1 [available at http://aaojournal.org]), which showed retinal flecks and areas of well-defined atrophy, typical aspects of Stargardt`s disease.3,4 The sequence analysis showed a homozygous nucleotide substitution in exon 9 of the ABCC6 gene (C1132T) introducing a stop codon at position 378 (Q378X). Login to comment

PMID: 17617515 [PubMed] Pfendner EG et al: "Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum."

No. Sentence Comment

254 Collectively, the mutations in exons 24 and 28, including the common mutations R1141X and del 23-29, accounted for 71.5% of all the 316 mutations identified in this study (table 2), and the 11 most prevalent mutations (R1141X, del23-29, R1339C, R1164X, 2787+1GRT, G1302R, R1138Q, R1138W, Q378X, R1314W, R518Q) accounted for 70% (223 of 316) of the mutant alleles identified (table 2). Login to comment
262 Genotype-phenotype correlations The comparison of subjects whose mutations would probably have resulted in no functional protein with those whose mutations would probably have resulted in some functional Table 2 Distinct mutations identified in the international case series of 271 patients with PXE Nucleotide change*À Predicted consequenceÀ Frequency (alleles) Exon-intron location Domain affected` Mutant alleles (%) References1 c.105delA p.S37fsX80 2 2 0.6 28 c.177-185del9 p.R60_Y62del 1 2 0.3 9, 28 c.179del12ins3 p. R60_W64del L60_R61ins 1 2 0.3 c.220-1gRc SJ 1 IVS 2 0.3 c.724gRt p.E242X 1 7 0.3 c.938insT FS 1 8 0.3 25 c.998+2delT SJ 1 IVS 8 0.3 2, 21 c.998+2del2 SJ 1 IVS 8 0.3 18 c.951cRg p.S317R 2 9 TM6 0.6 28 c.1087cRt p.Q363X 1 9 0.3 c.1091gRa p.T364R 1 9 TM7 0.3 9, 19, 21, 28 c.1132cRt p.Q378X 4 9 1.2 9, 17-19, 28, 37 c.1144cRt p.R382W 2 9 IC4 0.6 c.1171aRg p.R391G 3 9 IC4 0.9 9, 18, 28, 37 c.1176gRc p.K392N 1 9 IC4 0.3 c.1388tRa p.L463H 1 11 TM9 0.3 c.1484tRa p.L495H 1 12 IC5 0.3 28 c.1552cRt p.R518X 2 12 0.6 18, 19, 27, 28, 37 c.1553gRa p.R518Q 4 12 IC5 1.2 18, 19, 24, 28, 31 c.1603tRc p.S535P 1 12 TM10 0.3 c.1703tRc p.F568S 1 13 TM11 0.3 24 c.1798cRt p.R600C 1 14 TM11 0.3 c.1857insC FS 1 14 0.3 c.1987gRt p.G663C 1 16 NBF1 0.3 c.1999delG FS 1 16 0.3 c.2070+5GRA SJ 2 IVS 16 0.6 c.2093aRc p.Q698P 2 17 NBF1 0.6 c.2097gRt p.E699D 1 17 NBF1 0.3 c.2177tRc p.L726P 1 17 NBF1 0.3 c.2237ins10 FS 2 17 0.6 c.2252tRa p.M751K 1 18 NBF1 0.3 20, 37 c.2263gRa p.G755R 2 18 NBF1 0.6 c.2278cRt p.R760W 3 18 NBF1 0.9 20, 28, 32, 37 c.2294gRa p.R765Q 2 18 NBF1 0.6 20-22, 25, 28, 32, 37 c.2329gRa p.D777N 1 18 NBF1 0.3 c.2359gRt p.V787I 1 18 NBF1 0.3 c.2432cRt p.T811M 1 19 IC6 0.3 6 c.2643gRt p.R881S 1 20 IC6 0.3 c.2787+1GRT SJ 9 IVS 21 2.8 17, 20, 24, 28, 31, 37 c.2814cRg p.Y938X 1 22 0.3 c.2820insC FS 1 22 0.3 c.2831cRt p.T944I 1 22 TM12 0.3 c.2848gRa p.A950T 1 22 TM12 0.3 c.2974gRc p.G992R 1 22 TM13 0.3 2, 42 c.3340cRt p.R1114C 2 24 IC8 0.6 19, 28, 32, 37, 41 c.3389cRt p.T1130M 3 24 IC8 0.9 18, 19, 21, 22, 28, 30, 32, 37, 41 c.3398gRc p.G1133A 1 24 IC8 0.3 c.3412gRa p.R1138W 7 24 IC8 2.2 28, 30, 37 c.3413cRt p.R1138Q 7 24 IC8 2.2 18, 19, 24, 25, 28, 30, 32, 37, 41 c.3415gRa p.A1139T 2 24 IC8 0.6 c.3415gRa & c.2070+5GRA* p.A1139T & SJ 1 24, IVS 16 IC8 0.3 c.3415gRa & c.4335delG* p.A1139T & FS 1 24, 30 IC8 0.3 c.3421cRt p.R1141X 92 24 29.3 5, 9, 15,18, 19, 21, 22, 24, 28, 30-32, 33, 37, 41 c.3427cRt p.Q1143X 1 24 0.3 c.3490cRt p.R1164X 15 24 4.7 18, 27, 28, 31, 33 c.3491gRa p.R1164Q 1 24 IC8 0.3 28 c.3661cRt p.R1221C 1 26 IC9 0.3 21, 22, 28, 29 c.3662gRa p.R1221H 2 26 IC9 0.6 40 c.3676cRa p.L1226I 1 26 IC9 0.3 c.3722gRa p.W1241X 2 26 0.6 c.3774insC FS 2 27 0.6 c.3775delT p.G1259fsX1272 3 27 0.9 15, 25, 28, 41 c.3880-3882del p.K1294del 1 27 0.3 c.3883-5GRA SJ 1 IVS 27 0.3 c.3892gRt p.V1298F 1 28 NBF2 0.3 25 c.3904gRa p.G1302R 7 28 NBF2 2.2 21, 22, 25, 28 c.3907gRc p.A1303P 1 28 NBF2 0.3 21, 22, 25, 28 c.3912delG FS 1 28 0.3 28 c.3940cRt p.R1314W 4 28 NBF2 1.2 24, 25, 32, 36 c.3941gRa p.R1314Q 1 28 NBF2 0.3 25, 28, 32, 36, 41 c.4004tRa p.L1335Q 1 28 NBF2 0.3 c.4015cRt p.R1339C 16 28 NBF2 5.0 19, 25, 28, 33 c.4016gRa p.R1339H 2 28 NBF2 0.6 c.4025tRc p.I1342T 1 28 NBF2 0.3 protein did not yield significant differences. Login to comment

PMID: 18253096 [PubMed] Plomp AS et al: "ABCC6 mutations in pseudoxanthoma elasticum: an update including eight novel ones."

No. Sentence Comment

218 A novel Q378X mutation exists in the transmembrane transporter protein ABCC6 and its pseudogene: implications for mutation analysis in pseudoxanthoma elasticum. J Mol Med 2001; 79:536-46. Login to comment

PMID: 18791038 [PubMed] Symmons O et al: "How segmental duplications shape our genome: recent evolution of ABCC6 and PKD1 Mendelian disease genes."

No. Sentence Comment

350 A novel Q378X mutation exists in the transmembrane transporter protein ABCC6 and its pseudogene: implications for mutation analysis in pseudoxanthoma elasticum. 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

62 Table 1 Main characteristics of dermal fibroblasts derived from PXE patients and healthy controls used in the present study Sample ID Gender Agea Biopsy source ABCC6 genotypeb Statusc Age at disease onseta Number of involved organs PXE patients P60F Female 58 Axilla c.37-1G4A (SSM) c.37-1G4A (SSM) hm 56 3 P229F Female 50 NA c.1171A4G (p.R391G) c.1208C4A (p.A413N) c.2252T4A (p.M751K) cht NA NA P265F Female 62 Cervix c.1132C4T (p.Q378X) c.3421C4T (p.R1141X) cht 16 3 P3M Male 57 Cervix c.3421C4T (p.R1141X) c.3883-6G4A (SSM) cht 46 5 P128M Male 51 Cervix c.3769_3770insC (p.L1259fsX1277) c.3769_3770insC (p.L1259fsX1277) hm 48 3 P308M Male 42 NA c.3421C4T (p.R1141X) c.-90ins14 (c)ht NA NA P341M Male 41 NA c.1552C4T (p.R518X) ND ht NA NA Healthy controls F37A Female 37 Abdomen - - - wt - - F42A Female 42 Abdomen - - - wt - - F52C Female 52 Cheek - - - wt - - M2FS Male 2 Foreskin - - - wt - - M45D Male 45 Face - - - wt - - M56D Male 56 Face - - - wt - - hm, homozygote; cht, compound heterozygote; ht, heterozygote; wt, wild type; SSM, splice site mutation; NA, not applicable; ND, nondetected. Login to comment

PMID: 20075945 [PubMed] Costrop LM et al: "Novel deletions causing pseudoxanthoma elasticum underscore the genomic instability of the ABCC6 region."

No. Sentence Comment

211 23 Cai, L., Lumsden, A., Guenther, U. P., Neldner, S. A., Zach, S., Knoblauch, H. et al. A novel Q378X mutation exists in the transmembrane transporter protein ABCC6 and its pseudogene: implications for mutation analysis in pseudoxanthoma elasticum. J. Mol. Med. 79, 536-546 (2001). Login to comment

PMID: 21167005 [PubMed] Larusso J et al: "Pseudoxanthoma elasticum: a streamlined, ethnicity-based mutation detection strategy."

No. Sentence Comment

23 Two mutations seem to be present worldwide without evidence of a founder effect, p.Q378X and p.R1339C, suggesting the presence of mutational hotspots. Login to comment
42 A total of eight recurrent mutations were distinguished in the cohort, including nonsense (p.Q378X and p.R1141X), missense (p.R1138W and p.R1339C), splice site (3736-1G/A, 2787 + 1G/T), frameshift (2542 delG), and multiexon deletion (del exon 23-29). Login to comment
53 Two additional core mutations established in Mediterraneans and Scandinavians were p.Q378X and p.R1339C. Login to comment
55 p.Q378X distributed in 3.8% of Mediterraneans and 9.1% of Scandinavians. Login to comment
56 We did not identify p.Q378X in the French Canadian population, but it did appear in Northern Europeans (3.8%) and Asians (0.8%). Login to comment
81 p.R1339C appeared in Northern Europeans and Scandinavians, whereas p.Q378X was presentworldwide.Thesplicesitemutation2787+1G/Twasfound in French Canadians and Northern Europeans. Login to comment

PMID: 16763870 [PubMed] Ladewig MS et al: "[Pseudoxanthoma elasticum]."

No. Sentence Comment

272 Internetadressen PXE-Selbsthilfegruppe Deutschland : http://www.pxe-groenblad.de PXE International: http://www.pxe.org Tabelle 5 PXE verursachende Mutationen imabcc6-Gen Klassifikation Lokalisation Gen Protein Missense Exon 9 Exon 9 Exon 10 Exon 10 Exon 11 Exon 12 Exon 13 Exon 14 Exon 16 Exon 18 Exon 18 Exon 18 Exon 18 Exon 19 Exon 19 Exon 19 Exon 22 Exon 24 Exon 24 Exon 24 Exon 24 Exon 24 Exon 24 Exon 24 Exon 24 Exon 24 Exon 25 Exon 26 Exon 26 Exon 26 Exon 28 Exon 28 Exon 28 Exon 28 Exon 28 Exon 28 Exon 28 Exon 28 Exon 28 Exon 28 Exon 28 Exon 28 Exon 28 Exon 29 Exon 29 Exon 29 Exon 29 Exon 29 Exon 30 Exon 30 Exon 30 c.1091CaG c.1171AaG c.1233TaG c.1318TaG c.1363GaC c.1553GaA c.1703TaC c.1798CaT c.2018TaC c.2252TaA c.2278CaT c.2294GaA c.2297CaA c.2428GaA c.2458GaC c.2552TaC c.2855TaG c.3340CaT c.3341GaA c.3341GaC c.3362CaG c.3380CaT c.3389CaT c.3412CaT c.3413GaA c.3413GaC c.3608GaA c.3661CaT c.3712GaC c.3715TaC c.3892GaT c.3902CaT c.3904GaA c.3907GaC c.3932GaA c.3940CaT c.3941GaA c.3961GaA c.3976GaA c.4004TaC c.4015CaT c.4036CaT c.4041GaC c.4060GaC c.4069CaT c.4081GaA c.4182GaT c.4198GaA c.4209CaA c.4271TaC c.4377CaT p.T364R p.R391G p.N411K p.C440G p.A455P p.R518Q p.F568S p.R600G p.L673P p.M751K p.R760W p.R765Q p.A766D p.V810M p.A820P p.L851P p.F952C p.R1114C p.R1114H p.R1114P p.S1121W p.M1127T p.T1130M p.R1138W p.R1138Q p.R1138P p.G1203D p.R1221C p.D1238H p.Y1239H p.V1298F p.T1301I p.G1302R p.A1303P p.G1311E p.R1314W p.R1314Q p.G1321S p.D1326N p.L1335P p.R1339C p.P1346S p.Q1347H p.G1354R p.R1357W p.D1361N p.K1394N p.E1400K p.S1403R p.I1424T p.R1459C Klassifikation Lokalisation Gen Protein Nonsense Exon 9 Exon 12 Exon 17 Exon 18 Exon 23 Exon 24 Exon 24 Exon 26 Exon 26 Exon 27 Exon 29 c.1132CaT c.1552CaT c.2247CaT c.2304CaA c.3088CaT c.3421CaT c.3490CaT c.3668GaA c.3709CaT c.3823CaT c.4192CaT p.Q378X p.R518X p.Q749X p.Y768X p.R1030X p.R1141X p.R1164X p.W1223X p.Q1237X p.R1275X p.R1398X Spleißstellen Intron 21 Intron 25 Intron 26 c.2787+1GaT c.3634-3CaA c.3736-1GaA Insertion Exon 8 Exon 25 Exon 30 c.938-939insT c.3544dupC c.4220insAGAA Deletion Exon 2 Exon 2 Exon 3 Exon 8 Exon 9 Exon 16 Exon 16 Exon 18 Exon 19 Exon 22 Exon 27 Exon 29 Exon 29 Exon 30 Exon 31 c.179del9 c.179-195del c.220-222del c.960delC c.1088-1120del c.1944del22 c.1995delG c.2322delC c.2542delG c.2835-2850del16 c.3775delT c.4101delC c.4182delG c.4318delA c.4434delA Intragenische Deletion Exon 15 Exon 18 Exon 23-29 delEx15 delEx18 delEx23-29 Intergenische Deletion ABCC6 delABCC6 Fazit für die Praxis Eine spezifische Behandlung der Grunderkrankung ist nicht bekannt. 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

82 Summary of ABCC6/MRP6 mutations identified in German PXE patients Change in Number of Allelic frequency Exona nucleotideb Amino acid Statusc families in blood donorsd Referenceg i-1e c.37-1G>Af altered splicing hm 1 0 / 200 This study 2 c.113G>C p.W38S ht 1 0 / 200 This study i-3 c.346-6G>A altered splicing ht 2 Nd A, B 7 c.754C>T p.L252F ht 1 0 / 200 This study 9 c.1132C>T p.Q378X ht 4 Nd B, C 9 c.1171A>G p.R391G ht 1 Nd B, D 10 c.1244T>C p.V415A ht 1 0 / 200 This study 12 c.1460G>A p.R487Q ht 1 0 / 200 This study 12 c.1491C>A p.N497K ht 1 0 / 200 This study 12 c.1552C>T p.R518X ht 1 Nd B, E i-12 c.1574_1575insG p.L525fsX73 ht 1 0 / 200 This study 16 c.1995delG p.A667fsX20 ht 3 Nd A, F, G 18 c.2252T>A p.M751K ht 3 Nd F, G 18 c.2278C>T p.R760W ht 2 Nd B, F, G Change in Number of Allelic frequency Exona nucleotideb Amino acid Statusc families in blood donorsd Referenceg 18 c.2294G>A p.R765Q ht 2 Nd A, F, G, H 19 c.2552T>C p.L851P ht 1 Nd F i-21 c.2787+1G>T altered splicing ht 7 Nd B, C, F, I, J 22 c.2835_2850del16 p.P946fsX17 ht 1 Nd F 22 c.2855T>G p.F952C ht 1 Nd F 23 c.3145T>G p.S1049A ht 1 0 / 200 This study 23 c.3188T>G p.L1063R ht 1 0 / 200 This study 24 c.3340C>T p.R1114C ht 1 Nd B, K, G, L 24 c.3341G>A p.R1114H ht 1 Nd G, H, L, M 24 c.3389C>T p.T1130M ht 1 Nd B, D, G, H, K, L, M, N 24 c.3413G>A p.R1138Q ht 1 Nd A, B, D, J, K, L, N 24 c.3412C>T p.R1138W ht 1 Nd N 24 c.3421C>T p.R1141X hm, ht 26 Nd B, G, J, K, L, M, N, O, P, Q, R, S i-24 c.3505_3506+2delA GGT altered splicing ht 1 0 / 200 This study i-24 c.3507-3C>T altered splicing ht 2 Nd B 26 c.3715T>C p.Y1239H ht 1 Nd L 26 c.3723G>C p.W1241C ht 1 Nd A, L i-26 c.3736-1G>A altered splicing ht 1 Nd B, L, N 27 c.3775delT p.W1259fsX13 ht 1 Nd B, J, L, O i-27 c.3883-6G>A altered splicing ht 1 Nd B 28 c.3902C>T p.T1301I ht 1 Nd A, G, L 28 c.3932G>A p.G1311E ht 1 Nd L 28 c.3940C>T p.R1314W ht 1 Nd A, G, L 28 c.3941G>A p.R1314Q ht 1 Nd A, B, G, L 29 c.4182delG p.N1394fsX8 ht 2 Nd G, H, L 30 c.4209C>A p.S1403R ht 1 Nd F 31 c.4434delA p.R1479fsX25 hm 1 Nd F 23-29 Ex23_Ex29del p.A999_S1403del ht 5 Nd A, B, D, E, G, H, O, R a The exon that contains the ABCC6 sequence variation. Login to comment
89 Genotypes and phenotypes of the PXE patients analyzed in this study Phenotype Genotypeb No.a Sex, Age Age on diagnosis Organ involvement Mutations 1 M 36 11 E, S, G p.R1141X p.R1141X 2 F 44 39 E, S, G, A p.R1141X Ex23_Ex29del 3 F 41 7 E, S p.R1141X p.R1141X 4 F 46 19 E, S, A p.R1141X p.R1141X 5 F 59 55 E, S, A c.37-1G>A c.37-1G>A 6c F 63 16 E, S, H, V, A Ex23_Ex29del c.4182delG 7 F 24 15 E, S c.4434delA c.4434delA 8 M 60 23 E, S p.Q378X p.R1141X 9 F 79 65 E, S, A c.2787+1G>T p.R1141X 10 F 55 35 E, S, G, H, V, A p.Q378X c.2787+1G>T 11 F 47 14 S c.1995delG c.2787+1G>T 12c F 36 24 E, S c.2787+1G>T c.4182delG 13 F 56 8 E, S p.R1141X c.3507-3C>T 14 M 72 55 E, S, H, V p.R1141X 15 F 69 51 E, S c.1995delG p.R765Q 16 F 19 11 S p.R760W p.R1141X 17c F 59 50 E, S, H, V, A p.R1141X p.G1311E 18c M 54 32 E, S p.R1141X p.Y1239H 19-1 M 63 53 E, H p.L252F p.V415A p.R765Q 19-2 F 58 48 E, S p.L252F p.V415A p.R765Q 20 M 54 44 E, S, V, A c.3775delT c.346-6G>A 21 M 52 43 E, S, A p.R1141X c.3883-6G>A 22-1 M 47 36 E, S, G, H, V p.R518X 22-2 M 45 34 E, S, H p.R518X 23 F 35 22 E, S, A p.W38S 24 F 40 30 E c.346-6G>A 25-1 M 58 46 E, S, A p.R1141X c.3883-6G>A 25-2 M 19 10 S p.R1141X c.3883-6G>A 26-1 F 46 18 E, S, V p.R487Q c.3883-6G>A 27c F 62 30 E, S, A p.Q378X p.R1114H 28 F 59 49 E, A p.R1314Q c.3507-3C>T 29c F 30 10 E, S c.1995delG p.R1114C 30 M 67 52 E p.L1063R p.R1141X 31 F 50 46 E, S, V p.M751K p.R1141X 32 F 27 24 S Ex23_Ex29del 33c F 34 19 E, S Ex23_Ex29del p.T1130M 34 F 33 19 E, S c.2787+1G>T p.W1241C 35 M 47 15 E, S, G, H, V, A Ex23_Ex29del 36 M 72 63 E, S p.S1049A c.3736-1G>A p.S1403R 37 F 34 16 E, S c.2787+1G>T 38 F 42 8 E, S, V p.R1141X p.R1314W 39 F 37 20 E, S p.N497K 40 F 54 33 E, S, V, A p.M751K p.R1141X 41 M 53 49 E, S, G, H, V p.R1141X 42-1 F 52 38 E, S p.R391G p.R1141X 42-2 F 43 28 E, S p.R391G p.R1141X 43 F 64 58 S, A 44-1 F 51 27 E, S, A p.R1141X 44-2 F 18 9 E, S 44-3 F 54 26 E, S, V, A p.R1141X 45-1 F 64 49 E, S, G, V p.R1138Q 45-2 F 62 48 E, S, A p.R1138Q 46 M 56 25 E, S, V p.R1141X p.T1301I 47 F 34 23 E, S p.R760W c.2787+1G>T 48 M 47 24 E, S, V, A c.2835_2850del16 p.F952C p.R1141X 49 F 28 11 E, S, G, V p.M751K p.R1141X 50 F 39 25 E, S, V p.L851P p.R1141X c.3505_3506+2 delAGGT 51 F 61 16 E, S, H, A p.Q378X p.R1141X 52-1 F 40 20 E, S p.R1138W p.R1141X 52-2 F 43 23 E, S p.R1138W p.R1141X 53 M 68 66 E, H, V, G, A c.1574_1575insG p.R1141X F = female, M = male, wt = wild-type, hm = homozygote, ht = heterozygote, cht = compound heterozygote, nd = not determined, MSM = microsatellite marker, E = eyes, S = skin, G = gastrointestinum, H = heart, V = vascular tissue and A = arterial hypertension. Login to comment

PMID: 17693525 [PubMed] Zarbock R et al: "Pseudoxanthoma elasticum: genetic variations in antioxidant genes are risk factors for early disease onset."

No. Sentence Comment

142 b Patients who are (a) homozygous for PXE mutation p.R1141X, c.2787 ϩ 1GϾT, or c.4434delA; and (b) compound heterozygotes for 2 of the PXE mutations p.R1141X, c.2787 ϩ 1GϾT, Ex23_Ex29del, c.4182delG, p.Q378X, c.1995delG, p.E507X, and c.2835_2850del16. Login to comment

PMID: 19054062 [PubMed] Li Q et al: "Pseudoxanthoma elasticum: clinical phenotypes, molecular genetics and putative pathomechanisms."

No. Sentence Comment

68 Identification of additional recurrent nonsense mutations (p.Q378X in exon 9, p.R518X in exon 12 and p.R1164X in exon 24) as well as clustering of the missense mutations to exons 24 and 28 corresponding to the NBFs that are critical for the ATP binding and hydrolysis have allowed the development of streamlined mutation detection strategies to facilitate identification of mutations in the ABCC6 gene with the overall detection rate of up to 99% (for review see reference 26). Login to comment

PMID: 23702584 [PubMed] Zhou Y et al: "Premature termination codon read-through in the ABCC6 gene: potential treatment for pseudoxanthoma elasticum."

No. Sentence Comment

38 Different pseudoxanthoma elasticum (PXE)- associated nonsense mutations tested for PTC124 read-through Mutation Nucleotide sequence1 Location (exon) Mutation frequency (%)2 p.R1141X TGA-A 24 54 p.R1164X TGA-C 24 10 p.R518X TGA-G 12 1.2 p.R1398X TGA-G 29 1.2 p.Q378X TAG-A 9 o1 p.Q1143X TAG-G 24 o1 p.R1275X TGA-C 27 o1 1 The sequence depicts the stop codon (bold) followed by the nucleotide shown. Login to comment

PMID: 25367056 [PubMed] Giovannoni I et al: "Heart transplant and 2-year follow up in a child with generalized arterial calcification of infancy."

No. Sentence Comment

56 A compound heterozygosity was identified in ABCC6: the mutations were located at nucleotide position c.1132C>T (p.Q378X) and c.3421C>T (p.R1141X). Login to comment
58 Segregation analysis showed a compound heterozygous mutations with c.1132C>T (p.Q378X) and del_24-27 in the mother and a double heterozygous mutations c.1132C>T (p.Q378X) and c.3421C>T (p.R1141X) in the father. Login to comment
85 Fig. 2 Pedigree and haplotype analysis with markers from the ABCC6 regions: a double mutation on the same allele in cis (p.Q378X, p.R1141X) was found in the father and a mutation on the other allele in trans (p.Q378X, del_24-27) was found in the mother, affected by PXE (asterisk); the patient showed a compound heterozygous mutations of p.Q378X, p.R1141X, and del_24-27 Conclusions In this child with GACI and end-stage myocardial ischemia, the transplant solved the heart failure as observed throughout the 2-year follow-up and no new calcifications have been observed at the cardiac level (no coronary deposits). Login to comment