ABCMdb

PMID: 12151438

Wang Z, Milunsky J, Yamin M, Maher T, Oates R, Milunsky A
Analysis by mass spectrometry of 100 cystic fibrosis gene mutations in 92 patients with congenital bilateral absence of the vas deferens.
Hum Reprod. 2002 Aug;17(8):2066-72., [PubMed]

Sentences

No. Mutations Sentence Comment

20 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly1244Glu ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Trp1316* ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Asp1270Asn ABCC7 p.Ser1251Asn ABCC7 p.Arg352Gln ABCC7 p.Ile148Thr ABCC7 p.Glu585* ABCC7 p.Leu206Trp ABCC7 p.Gln493* ABCC7 p.Val520Phe ABCC7 p.Gly85Glu ABCC7 p.Tyr122* ABCC7 p.Arg560Thr ABCC7 p.Arg117Leu ABCC7 p.Thr338Ile ABCC7 p.Met1101Lys ABCC7 p.Arg1070Gln ABCC7 p.Ser1235Arg ABCC7 p.Arg1066Cys ABCC7 p.Ser1255* ABCC7 p.Ser945Leu ABCC7 p.Gln552* ABCC7 p.Arg1283Met ABCC7 p.Lys710* ABCC7 p.Tyr563Asn ABCC7 p.Gln890* ABCC7 p.Trp1089* ABCC7 p.Arg75* ABCC7 p.Leu1077Pro ABCC7 p.Gly480Cys ABCC7 p.Ser1196* ABCC7 p.Ile336Lys ABCC7 p.Glu60* ABCC7 p.Arg560Lys ABCC7 p.Arg553Gly ABCC7 p.Thr360Lys ABCC7 p.Gln493Arg ABCC7 p.Tyr563Asp ABCC7 p.Gln1238* ABCC7 p.Cys524* ABCC7 p.Gln359Lys ABCC7 p.Ser364Pro ABCC7 p.Gly330* ABCC7 p.Ala559Thr ABCC7 p.Lys1177Arg ABCC7 p.Ala561Glu ABCC7 p.Arg1070Pro ABCC7 p.Trp1282Arg Given the frequency of CF mutations, especially in the Caucasian population ( in 25), and the common request by CBAVD men to sire their own offspring by using surgical Table I. The 100 most common cystic fibrosis mutations listed by exon Mutationa Exonb Frequency (%)c G85E 3 0.1 394delTT 3 Swedish E60X 3 Belgium R75X 3 405ϩ1G→A Int 3 R117H 4 0.30 Y122X 4 French 457TAT→G 4 Austria I148T 4 Canada (French Canadian) 574delA 4 444delA 4 R117L 4 621ϩ1G→T Int 4 0.72 711ϩ1G→T Int 5 Ͼ0.1 712-1G→T Int 5 711ϩ5G→A Int 5 Italy (Caucasian) L206W 6a R347P 7 0.24 1078delT 7 Ͼ0.1 R334W 7 Ͼ0.1 1154InsTC 7 T338I 7 Italy R347H 7 Turkey Q359K/T360K 7 Israel (Georgian Jews) I336K 7 R352Q 7 G330X 7 S364P 7 A455E 9 0.20 I507 10 0.21 F508 10 66.02 1609delCA 10 Spain (Caucasian) V520F 10 Q493X 10 C524X 10 G480C 10 Q493R 10 1717-1G→A Int 10 0.58 R553X 11 0.73 G551D 11 1.64 G542X 11 2.42 R560T 11 Ͼ0.1 S549N 11 Q552X 11 Italy S549I 11 Israel (Arabs) A559T 11 African American R553G 11 R560K 11 1812-1G→A Int 11 A561E 12 E585X 12 Y563D 12 Y563N 12 1898ϩ1G→A Int 12 0.22 1898ϩ1G→C Int 12 2183AA→G 13 Italian 2184delA 13 Ͻ0.1 K710X 13 2143delT 13 Moscow (Russian) 2184InsA 13 1949del84 13 Spain (Spanish) 2176InsC 13 2043delG 13 2307insA 13 2789ϩ5G→A Int 14b Ͼ0.1 2869insG 15 S945L 15 Q890X 15 3120G→A 16 2067 Table I. continued Mutationa Exonb Frequency (%)c 3120ϩ1G→A Int 16 African American 3272-26A→G Int 17a R1066C 17b Portugal (Portugese) L1077P 17b R1070Q 17b Bulgarian W1089X 17b M1101K 17b Canada (Hutterite) R1070P 17b R1162X 19 0.29 3659delC 19 Ͼ0.1 3849G→A 19 3662delA 19 3791delC 19 3821delT 19 Russian Q1238X 19 S1235R 19 France, South S1196X 19 K1177R 19 3849ϩ10kbC→T Int 19 0.24 3849ϩ4A→G Int 19 W1282X 20 1.22 S1251N 20 Dutch, Belgian 3905insT 20 Swiss, Acadian, Amish G1244E 20 R1283M 20 Welsh W1282R 20 D1270N 20 S1255X 20 African American 4005ϩ1G→A Int 20 N1303K 21 1.34 W1316X 21 aMutations were chosen according to their frequencies (Cystic Fibrosis Genetic Analysis Consortium, 1994; Zielenski and Tsui, 1995; Estivill et al., 1997). Login to comment 34 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Arg560Thr ABCC7 p.Arg117Leu ABCC7 p.Arg1283Met ABCC7 p.Arg560Lys ABCC7 p.Arg1283Lys ABCC7 p.Arg553Gly The mutations in the 25 mutation panel were: ∆F508, G542X, N1303K, G551D, W1282X, 1717-1G→A, R553X, 621ϩ1G→T, R1162X, 2183AA→G, R117H, ∆I507, R560T, 3849ϩ10kbC→T, S549N, S549I, S549R, R1283M, R1283K, R553G, R560K, R117L, 1774delCT, 1811ϩ1G→C, and 4006-61del14. Login to comment 35 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Ile148Thr ABCC7 p.Gly85Glu ABCC7 p.Arg560Thr ACMG 25 mutation panel (ACMG25): The following mutations are the recommended core mutations for general population CF carrier screening by American College of Medical Genetics (ACMG) (Grody, et al 2001): ∆F508, G542X, N1303K, G551D, W1282X, 1717-1G→A, R553X, 621ϩ1G→T, R1162X, R117H, ∆I507, 1898ϩ1G→A, G85E, R347P, A455E, R560T, R334W, 3849ϩ10kbC→T, 3659delC, 1078delT, 2789ϩ5G→A, 711ϩ1G→T, 2184delA, 3120ϩ1G→A and I148T. Login to comment 76 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Leu206Trp After the 5T allele, the relative frequent mutations with two to four alleles were: R117H (four alleles), W1282X (four alleles), G551D (three alleles), L206W (three alleles) and D1270 (two alleles). Login to comment 83 ABCC7 p.Gln493* ABCC7 p.Arg1066Cys Matrix-assisted laser desorption ionization-time of flight mass spectra for multiplex primer oligonucleotide base extension reactions of mutations ∆F508, Q493X and R1066C. Login to comment 86 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Asp1270Asn ABCC7 p.Leu206Trp ABCC7 p.Gln890* CFTR mutations in 92 men with congenital bilateral absence of vas deferens Mutations CFTR mutation panels CF25 CF25 ϩ 5T ACMG25 ACMG25 ϩ 5T CF100 Mutations detected in ∆F508 39 39 39 39 39 CF25 mutation panel R117H 4 4 4 4 4 W1282X 4 4 4 4 4 G551D 3 3 3 3 3 G542X 1 1 1 1 1 N1303K 1 1 1 1 1 IVS8-polyT IVS8-5T 33 33 33 Additional mutations L206W 3 detected not in CF25 D1270N 2 mutation panel 1154InsTC 1 3272-26A→G 1 A455E 1 1 1 R334W 1 1 1 Q890X 1 Total 14 52 85 54 87 95 respectively, in the total number of patients with at least one mutation. Login to comment 91 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Asp1270Asn ABCC7 p.Asp1270Asn ABCC7 p.Asp1270Asn ABCC7 p.Leu206Trp ABCC7 p.Leu206Trp ABCC7 p.Leu206Trp ABCC7 p.Gln890* ABCC7 p.Gln890* CFTR genotypes in 92 men with congenital bilateral absence of vas deferens Genotypesa CFTR mutation panelsb CF25 CF25 ϩ 5T ACMG25 ACMG25 ϩ 5T CF100 Two mutations ∆F508/5T 16 16 16 W1282X/5T 4 4 4 ∆F508/R117Hc 3 3 3 3 3 G542X/5T 1 1 1 G551D/5T 1 1 1 ∆F508/L206W 2 ∆F508/A455E 1 1 1 ∆F508/3272-26A→G 1 Q890X/5T 1 L206W/5T 1 D1270N/D1270N 1 5T/5T 1 1 1 Sub-total 3 26 4 27 33 One mutation ∆F508/ϩ 36 20 35 19 16 5T/ϩ 9 9 7 G551D/ϩ 3 2 3 2 2 G542X/ϩ 1 1 R117H/ϩ 1 1 1 1 1 N1303K/ϩ 1 1 1 1 1 W1282X/ϩ 4 4 R334W/ϩ 1 1 1 1154InsTC/ϩ 1 Sub-total 46 33 46 33 29 Total (%) 49 (53.3) 59 (64.1) 50 (54.3) 60 (65.2) 62 (67.4) No mutation (%) 43 (46.7) 33 (35.9) 42 (45.7) 32 (34.8) 30 (32.6) aMutations L206W, 3272-26A→G, Q890X, D1270N, 1154InsTC and 5T are not in either CF25 and ACMG25 panels, while A455E and R334W are not in CF25, but are part of ACMG25 panel. Login to comment 93 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Gly542* bThe increase in the number of patients with two mutations under CF25ϩ5T, ACMG25ϩ5T and CF100, compared with CF25 and ACMG25, was due to identification of a second mutation and reflected by the reduction of the number of patients with one mutation (e.g. ∆F508/ϩ, G551D/ϩ, G542X/ϩ, W1282X/ϩ). Login to comment 97 ABCC7 p.Asp1270Asn Two homozygotes for 5T and D1270N were also detected. Login to comment 100 ABCC7 p.Arg117His ABCC7 p.Trp1282* Two relatively frequent compound heterozygotes were F508/ R117H (3/33) and W1282X/5T (4/33). Login to comment 119 ABCC7 p.Arg117His The compound heterozygote ∆F508/R117H, previously reported to occur commonly in CBAVD patients (Dork et al., 1997), was also a frequent genotype (3/33) in this study. Login to comment 120 ABCC7 p.Arg117His It was noted that R117H occurred on two chromosomal backgrounds, one carrying a 5T allele in CF patients and the other carrying a 7T allele in CBAVD patients, when the other chromosome carries a severe mutation such as ∆F508 (Kiesewetter et al., 1993). Login to comment 123 ABCC7 p.Arg117His ABCC7 p.Arg117His Although it was not confirmed, our results indicate that ∆F508 and R117H were on chromosome backgrounds of 9T and 7T respectively, because at least one 9T allele was seen in each one of the 41 patients having a ∆F508 mutation, a 7T in each of the four patients with R117H mutation. Login to comment 125 ABCC7 p.Arg117His The association of R117H in cis with a 5T allele results in CF when patients carry in trans ∆F508 or one of the severe mutations, and probably represents a general theme that a splicing mutation such as 5T, in cis with a mild mutation, can aggravate that mild mutation. Login to comment 127 ABCC7 p.Leu206Trp L206W is another mild mutation reported with relatively high frequency in both CF and CBAVD patients (Chillon et al., 1995; Mak et al., 1999; Claustres et al., 2000) and which we noted in three compound heterozygotes, two with ∆F508 and one with 5T. Login to comment 128 ABCC7 p.Leu206Trp ABCC7 p.Leu206Trp ABCC7 p.Leu206Trp It appears that L206W is associated in cis with the 9T allele since both ∆F508/L206W patients have a homozygous 9T background, while 5T/L206W exists in a 5T/9T background. Login to comment