ABCMdb

PMID: 18157818

Vanakker OM, Leroy BP, Coucke P, Bercovitch LG, Uitto J, Viljoen D, Terry SF, Van Acker P, Matthys D, Loeys B, De Paepe A
Novel clinico-molecular insights in pseudoxanthoma elasticum provide an efficient molecular screening method and a comprehensive diagnostic flowchart.
Hum Mutat. 2008 Jan;29(1):205., [PubMed]

Sentences

No. Mutations Sentence Comment

28 ABCC6 p.Arg1141* One is the nonsense mutation c.3421C>T (p.R1141X), which, in a homozygous state, leads to complete loss of ABCC6 function and is more frequent among the European population [Chassaing et al., 2005]. Login to comment 78 ABCC6 p.Arg1141* Mutations were most frequently located in exons 24 (47%), mainly due to the p.R1141X mutation, 18 (8%), 28 (7%) and 29 (5%). Login to comment 80 ABCC6 p.Arg1141* The nonsense mutation c.3421C>T (p.R1141X) in exon 24 was most frequently found (31/76 alleles or 41%), both in homozygous (52%) and compound heterozygous (43%) state. Login to comment 83 ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1138Trp ABCC6 p.Arg518Gln ABCC6 p.Arg518Gln ABCC6 p.Arg1398* ABCC6 p.Gln1237* ABCC6 p.Ala1303Pro ABCC6 p.Ala1303Pro ABCC6 p.Ala1303Pro ABCC6 p.Thr1301Ile ABCC6 p.Gly1354Arg ABCC6 p.Gly1354Arg ABCC6 p.Gly1354Arg ABCC6 p.Arg1114His ABCC6 p.Glu1400Lys ABCC6 p.Met751Lys ABCC6 p.Met751Lys ABCC6 p.Arg1164Gln ABCC6 p.Arg1221His ABCC6 p.Glu125Lys ABCC6 p.Arg1339His ABCC6 p.Gly1263Arg ABCC6 p.Thr500Pro ABCC6 p.Gly666Val ABCC6 p.Thr364Met ABCC6 p.Asn793Leu ABCC6 p.Arg765Trp ABCC6 p.Asn466Tyr ABCC6 p.Ser398Arg ABCC6 p.Gly1405Ser ABCC6 p.Arg760Gln ABCC6 p.Arg760Gln ABCC6 p.Glu521Asp ABCC6 p.Gln981His ABCC6 p.Leu1025Pro Genotype and Phenotype of 42 Belgian PXE Patients Patient S e x Age/Clinical score at initial presentation Age/Clinical score at most recent follow-up Mutations* Allele 1 Allele 2 01-001 F 52 - S0, E2 65 - S0, E3, HT p.R1141X c.3421C>T p.R760Q c.2279G>A 02-001 M 18 - S1, E2, VR-I 18 - S1, E2, VR-I p.R1141X c.3421C>T p.R1141X c.3421C>T 03-001 F 59 - S1, E4 75 - S1, E4, HT, IC, VR-I p.R1141X c.3421C>T p.N793L c.2379C>G 04-001 F 36 - S3, E2 36 - S3, E2 p.N466Y c.1396A>T p.R1339H c.4016G>A 05-001 F 26 - S1, E4 43 - S3, E4, VR-I p.R1141X c.3421C>T p.T364M c.1091C>T 06-001 F 36 - S2, E4 44 - S2, E4, P p.A1303P c.3907G>C None found - 07-001 M 48 - S1, E2, HT 58 - S1, E4, HT p.R1141X c.3421C>T p.R1141X c.3421C>T 08-001 F 26 - S1, E0 44 - S2, E2 p.R1141X c.3421C>T p.R760Q c.2279G>A 09-001 M 49 - S0, E3, P, GIB 65 - S2, E4, P, HT, VR-I, GIB p.A1303P c.3907G>C None found - 10-001 F 46 - S1, E2 63 - S3, E4, HT, AP,VR-I p.R1141X c.3421C>T p.R1141X c.3421C>T 11-001 M 25 - S1, E2, GIB 37 - S1, E3, GIB p.R1141X c.3421C>T None found - 12-001 F 52 - S1, E4, CI, HT, VR-I 52 - S1, E4, IC, HT, VR-I p.R1141X c.3421C>T p.R1141X c.3421C>T 12-002 F 40 - S1, E2, HT, MVP, VR-I 40 - S1, E2, HT, MVP, VR-I p.R1141X c.3421C>T p.R1141X c.3421C>T 13-001 F 65 - S0, E2 80 - S0, E2, P, VR-I p.R1141X c.3421C>T p.R1141X c.3421C>T 13-002 F 57 - S3, E4 73 - S3, E4, HT, CI, VR-I p.R1141X c.3421C>T p.R1141X c.3421C>T 14-001 F 23 - S1, E2 27 - S1, E2 p.S398R c.1194C>G - c.3364delT 15-001 F 27 - S1, E2 27 - S1, E2 p.R1138W c.3412C>T p.R1221H c.3662G>A 16-001 M 51 - S2, E2 54 - S2, E2 p.R1141X c.3421C>T p.R1141X c.3421C>T 17-001 M 42 - S1, E3, IC 58 - S1, E3, IC Del23-29 - p.R518Q c.1553G>A 18-001 M 63 - S1, E4 63 - S1, E4 p.E1400K c.4198G>A None found - 19-001 F 34 - S2, E2 50 - S2, E2 p.A1303P c.3907G>C p.R1398X c.4192C>T 20-001 F 52 - S2, E2, HT, IC, GIB 68 - S2, E4, HT, IC, GIB p.R1141X c.3421C>T None found - 21-001 M 20 - S1, E2 26 - S1, E2 p.R1141X c.3421C>T p.R1141X c.3421C>T 22-001 M 53 - S2, E2, IC, AP 69 - S2, E2, HT, IC, AP p.M751K c.2252T>A p.R1164Q c.3491G>A 23-001 F 20 - S1, E2 27 - S1, E2, P, VR-I p.G666V c.1996G>T - c.1868-5T>G 24-001 M 54 - S1, E2 57 - S1, E2 p.T500P c.1498A>C p.E521D c.1563G>C 25-001 F 50 - S1, E3, HT, MI 57 - S2, E3, HT, MI p.R1141X c.3421C>T p.R1141X c.3421C>T 26-001 M 52 - S2, E4, HT 68 - S2, E4, HT, CI p.M751K c.2252T>A Del23-29 - 27-001 F 61 - S3, E4 68 - S3, E4, P, CI, AP p.R1141X c.3421C>T - c.4104delC Allele 2 28-001 F 31 - S1, E2 32 - S1, E2 - c.1674DelC p.R765W c.2293C>T Patient S e x Age/Clinical score at initial presentation Age/Clinical score at most recent follow-up Mutations* Allele 1 Allele 2 29-001 M 30 - S1, E3 32 - S1, E3 p.E125K c.373G>A p.L1025P c.3074T>C 30-001 M 65 - S0, E2, HT, CI, MI 66 - S0, E2, HT, CI, MI p.G1405S c.4213G>A None found - 31-001 F 38 - S1, E4 39 - S1, E4 p.R1141X c.3421C>T Del23-29 - 32-001 M 22 - S1, E2 36 - S1, E2 p.R1141X c.3421C>T p.R518Q c.1553G>A 33-001 F 45 - S2, E3, P 61 - S2, E3, P, VR-II p.R1141X c.3421C>T p.R1141X c.3421C>T 34-001 F 65 - S1, E4, HT 81 - S1, E4, HT, AP p.R1141X c.3421C>T p.T1301I c.3902C>T 35-001 F 62 - S2, E2 78 - S2, E2, HT - c.175_179del p.G1354R c.4060G>C 35-002 F 58 - S2, E2 74 - S2, E4 - c.175_179del p.G1354R c.4060G>C 35-003 M 67 - S2, E2 79 - S2, E3, HT, VR-I - c.175_179del p.G1354R c.4060G>C 36-001 M 53 - S1, E4 59 - S1, E4, HT, AP p.R1114H c.3341G>A p.Q1237X c.3709C>T 37-001 M 18 - S3, E2 18 - S3, E2 p.Q981H c.2943G>T - c.3507-3C>A 38-001 F 27 - S1, E2 27 - S1, E2 p.G1263R c.3787G>A - c.4182delG Table 1 represents the sex of all patients (M = male; F= female) and the age (in years - italics), respectively at initial presentation and last follow-up. Login to comment 127 ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* 12-001(II-1) C F I:1 I:2 II:1 II:2 II:3II:4 III:1 III:2 II:5 III:3 III:4 R1141X/ WT R1141X/ WT R1141X/ WT R1141X/ WT R1141X/ WT R1141X/ R1141X D E A B R1141X/ R1141X R1141X/ WT 12-002(II-3) Table 2. Prevalence of the Cutaneous (A) and Ocular (B) Manifestations of PXE in This Study at Initial Presentation and at Last Consultation Initial presentation Last consultation A. Login to comment 141 ABCC6 p.Arg1141* Especially in patients homozygous for the p.R1141X mutation - previously associated with a more severe phenotype [Hu et al., 2003]-, no significant difference with patients with either one or no nonsense mutation was observed. Login to comment 145 ABCC6 p.Arg1141* An initial analysis can be limited to the latter four exons (including p.R1141X) and the Del23-29 with a direct sequencing based approach. Login to comment