ABCMdb

PMID: 10875853

Casals T, Bassas L, Egozcue S, Ramos MD, Gimenez J, Segura A, Garcia F, Carrera M, Larriba S, Sarquella J, Estivill X
Heterogeneity for mutations in the CFTR gene and clinical correlations in patients with congenital absence of the vas deferens.
Hum Reprod. 2000 Jul;15(7):1476-83., [PubMed]

Sentences

No. Mutations Sentence Comment

30 ABCC7 p.Leu997Phe In order to compare the frequencies of ∆F508, L997F, 3732delA and(n ϭ 11) or left (n ϭ 13) side. Login to comment 55 ABCC7 p.Gly542* ∆F508 and G542X were the most frequently patients (30 CBAVD, 10 CUAVD) were reported previously (Casals identified CF mutations, but at lower frequencies than in CF et al., 1995). Login to comment 57 ABCC7 p.Arg117His ABCC7 p.Leu206Trp In contrast, mutations L206W and R117H, Molecular analysis of the CFTR gene was performed in all 134 each causing a mild CF phenotype (Dean et al., 1990; patients. Login to comment 59 ABCC7 p.Gly542* Mutations ∆F508 and in CAVD than in CF patients [4.0% versus 0.6% (χ2 ϭ 20.09, G542X (Kerem et al., 1989, 1990) were analysed in all patients, as P Ͻ 0.001) and 3.6% versus 0.3% (χ2 ϭ 28.45, P Ͻ 0.001)they are the most common mutations in Spanish CF patients, 53% respectively].and 8% respectively (Casals et al., 1997). Login to comment 62 ABCC7 p.Arg117His ABCC7 p.Gly542* ABCC7 p.Leu206Trp Recently, direct analysis of 31 CFTR mutations (PCR/OLA Cystic Fibrosis Assay; Perkin Elmer, Foster City) was 6(5T), ∆F508, G542X, L206W and R117H are the most performed in 30 of these infertile men. Login to comment 67 ABCC7 p.Ala1006Glu ABCC7 p.Asp110Tyr ABCC7 p.Ser50Pro ABCC7 p.Ser50Pro ABCC7 p.His484Tyr ABCC7 p.Gln890Arg ABCC7 p.Leu383Ser ABCC7 p.Pro1021Ser The abnormally migrating fragments were characterized by sequencing with the DyeDeoxy™ chain terminator method on an variant and another mutation (S50P, 2751ϩ3A→G, A1006E I. Description of the seven novel CFTR mutations and five polymorphisms in CAVD patients Mutation Location Nucleotide Amino acid Markers haplotype changes change (T)n-8CA-17bTA-M470V S50P exon 2 280 T→C Ser → Pro 5T/7T-16-31-ND D110Y exon 4 460 G→T Asp acid → Tyr 7T-17-7-V470 L383S exon 8 1280 T→C Leu → Ser 7T-16-7-M470 H484Y exon 10 1582 C→T His → Tyr no phase-M470 2751ϩ3A→G intron 14a 2751ϩ3 A→G - 5T-16-30-ND Q890R exon 15 2801 A→G Glu → Arg 7T-16-7/29-V470 P1021S exon 17a 3193 C→T Pro → Ser 7T-17-7-M470 Polymorphisms 104C/A 5ЈUTR - 296ϩ128G/C intron 3 - 741C/T exon 6a Ile203 no change 3195A/T exon 17a Pro1021 no change 3212T/C exon 17a Ile1027 no change CAVD ϭ congenital absence of the vas deferens; ND ϭ not determined; 5ЈUTR ϭ 5Ј untranslated region. Login to comment 70 ABCC7 p.Gly542* Thethe vas deferens M470V variant in exon 10 was analysed in 82 patients (98 Mutation CBAVD CUAVD Total alleles M470 and 66 V470), (TTGA)n in intron 6a which (n ϭ 42) 156 alleles (%) 14 alleles (%) 170 alleles (%) presented the higher frequency of seven repeats (129/272 alleles), T854T in exon 14a (72/272 alleles), 4521G→A in 5T 50a (32) 6 (43) 56 (33) exon 24 (62/272) and 3601-65C/A in intron 18 (48/272) were∆F508 40 (26) 3 (21) 43 (25) G542X 10 (6) 1 (7) 11 (6) the most frequent. Login to comment 71 ABCC7 p.Arg117His ABCC7 p.Leu206Trp ABCC7 p.Gly576Ala Six polymorphisms: 125G/C, 1525-61A/G, L206W 9 (6) 0 9 (5) 1898ϩ152T/A, 1716G/A, G576A and 875ϩ40A/G presented R117H 8 (5) 0 8 (5) frequencies of between 2.5% and 4.0%. Login to comment 72 ABCC7 p.Arg668Cys Another four with2789ϩ5G→A 4 (3) 0 4 (2) D1270NϩR74W 3 (2) 0 3 (2) frequencies of 1-2% were 1816G/A, 4404C/T, 1001ϩ11C/T 1949del84 2 (1) 0 2 (1) and R668C. Login to comment 73 ABCC7 p.Val232Asp ABCC7 p.Leu383Ser Finally, six polymorphisms were found each in V232D 2 (1) 0 2 (1) one patient: 104G/T, 296ϩ128G/C, 741C/T, 3195A/T, 3212T/3732delA 0 2 (14) 2 (1) L383S 1 1 (7) 2 (1) C and 4029A/G. Login to comment 74 ABCC7 p.Ala1006Glu ABCC7 p.Phe1074Leu The five new polymorphisms identified are Others (27) 27 (17) 1 (7) 28 (17) described in Table I. aS50P (n ϭ 1), 2751ϩ3A→G (n ϭ 1), F1074L (n ϭ 1), A1006E (n ϭ 2). Login to comment 77 ABCC7 p.Phe1074Leu Ten patients (five CUAVD, five CBAVD) had siblings who died during infancy of respiratoryand F1074L). Login to comment 78 ABCC7 p.Ser50Pro Except for the S50P mutation, which is associated to 5T and 7T alleles in CAVD patients, the other three infections. Login to comment 83 ABCC7 p.Val232Asp We detected only three homozygous patients (one for V232D P Ͻ 0.001). Login to comment 88 ABCC7 p.Leu997Phe Five of these patients (31%) carried one CFTR mutation, three being ∆F508, L997F are shown in Table V. Two men with CUAVD had unilateral cryptorchidism associated with ipsilateral inguinal hernia.or 3732delA, and two the 5T variant. Login to comment 91 ABCC7 p.Leu997Phe Nasal pathology was more frequent in CBAVD patients with mutations (36%) than in those without mutationsof these mutations in the general Spanish population (200 samples not CF) are ∆F508 2%, L997F 0.5%, 3732delA 0%, (8.3%). Login to comment 95 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Leu206Trp ABCC7 p.Met952Thr ABCC7 p.Asp110Tyr ABCC7 p.Ser50Pro ABCC7 p.Gln890Arg ABCC7 p.Leu383Ser ABCC7 p.Pro1021Ser CFTR genotypes in 24 patients with congenital unilateral absenceTable III. CFTR genotypes in 110 patients with congenital bilateral absence of the vas deferens of the vas deferens Mutations IVS8-6(T) n (%)Mutations IVS8-6(T) n (%) Two CFTR mutations 62 (56) Two CFTR mutations 5 (21) ∆F508/- 5T/9T 2 (8)∆F508/- 5T/9T 17 (15) G542X/- 5T/9T 6 (5) G542X/- 5T/9T 1 3732delA/- 5T/7T 1∆F508/L206W 9T/9T 6 (5) ∆F508/D1270NϩR74W 7T/9T 3 (3) L383S/- 5T/7T 1 One CFTR mutation 4 (17)∆F508/R117H 7T/7T 1 ∆F508/P1021S 7T/9T 1 ∆F508/-a 7T/9T 1 3732delA/-a 7T/7T 1∆F508/M952T 7T/9T 1 ∆F508/D110Y 7T/9T 1 Q890R/- 7T/7T 1 -/-a 5T/7T 1∆F508/S50P 5T/9T 1 ∆F508/2751ϩ3A→G 5T/9T 1 Negative CFTR mutations 15 (62) -/- 7T/7T 10 (42)G542X/R117H 7T/9T 1 G542X/2789ϩ5G→A 7T/9T 1 -/- 7T/9T 3 (12) -/- 9T/9T 2 (8)R117H/2789ϩ5G→A 7T/7T 1 R117H/712-1G→T 7T/9T 1 R117H/∆I507 7T/7T 1 aThree carrier patients with renal agenesis. Login to comment 96 ABCC7 p.Leu206Trp ABCC7 p.Leu206Trp ABCC7 p.Leu206Trp ABCC7 p.Ser50Pro ABCC7 p.Arg1070Trp L206W/- 5T/9T 1 L206W/3121-1G→A 7T/9T 1 L206W/1949del84 7T/9T 1 transrectal ultrasonography was significantly smaller in∆E115/S50P 7T/7T 1 2869insG/R1070W 7T/7T 1 CBAVD than in CUAVD (F ϭ 8.1, P ϭ 0.005). Login to comment 97 ABCC7 p.Arg258Gly ABCC7 p.Ser945Leu ABCC7 p.Val232Asp ABCC7 p.Val232Asp ABCC7 p.Ala1006Glu ABCC7 p.Leu383Ser ABCC7 p.Phe1074Leu Dilatation V232D/V232D 9T/9T 1 of ejaculatory ducts, often resembling utricular cysts, was S945L/R258G 7T/7T 1 demonstrable also in some men, all of whom were azoospermicG551D/F1074L 5T/7T 1 A1006E/L383S 5T/7T 1 (Figure 1). Login to comment 98 ABCC7 p.Ser549Arg ABCC7 p.Ser1235Arg ABCC7 p.Glu92Lys ABCC7 p.Lys1060Thr Vasograms performed in six patients with CUAVD E92K/- 5T/7T 1 not only confirmed ultrasonographic findings, but also showed 711ϩ1G→T/- 5T/7T 1 additional abnormalities at various levels of the seminal tract.R334W/- 5T/7T 1 S549R/- 5T/7T 1 The volume and consistency of testes was normal, except in 1949del84/- 5T/7T 1 patients with other concomitant pathologies, such as crypt- K1060T/- 5T/7T 1 orchidism (n ϭ 6), trauma (n ϭ 2), orchitis (n ϭ 2) orR1162X/- 5T/7T 1 S1235R/- 5T/7T 1 tumour (n ϭ 1). Login to comment 99 ABCC7 p.Ala1006Glu The prostate gland showed normal size and A1006E/- 5T/5T 1 morphology in all patients. Login to comment 101 ABCC7 p.Gly542* Azoospermia was more frequent in CUAVD ∆F508/- 9T/9T 3 (3) patients with CFTR mutations (7/9) than in those without-/- 5T/9T 2 (2) G542X/- 7T/9T 2 (2) mutations (8/13), and sperm concentration was higher in the 2789ϩ5G→A/- 7T/7T 2 (2) latter group. Login to comment 102 ABCC7 p.Arg117His However, the differences were not statistically R117H/- 7T/7T 2 (2) significant. Login to comment 103 ABCC7 p.His484Tyr Concentrations of citrate in seminal plasma showedR117H/- 7T/9T 1 H484Y/- 7T/9T 1 no significant differences between groups. Login to comment 104 ABCC7 p.Asn1303Lys ABCC7 p.Gly85Glu ABCC7 p.Tyr1014Cys In a small group of G85E/- 7T/7T 1 patients, alpha-glucosidase activity was 18.5 Ϯ 2.7 mU/ml in 2752-15C→G/- 7T/7T 1 CUAVD (n ϭ 4), and 26.7 Ϯ 5.5 mU/ml in CBAVD (n ϭ 7).L997F/-a 7T/7T 1 1677delTA/- 7T/7T 1 After reclassification of the patients according to the presence Y1014C/- 7T/9T 1 of zero, one or two mutations, none of the variables showed N1303K/- 7T/9T 1 significant differences either in CUAVD or CBAVD (notNegative CFTR mutation 16 (15) -/- 7T/7T 12 (11) shown). Login to comment 147 ABCC7 p.Leu383Ser (C) Transrectal ultrasonography of an azoospermic patient with right CUAVD and a CFTR genotype L383S/5T. Login to comment 180 ABCC7 p.Ala120Thr ABCC7 p.Gln30* It has been proposed that when renal anomalies coin the Spanish population: SSCP screening for 60 known mutations and exist with CAVD, a defect in the Wolffian duct is produced at identification of four new mutations (Q30X, A120T, 1812-1G→A and 3667del4). Login to comment 201 ABCC7 p.Leu206Trp Desgeorges, M., Dodier, M., Piot, M. et al. (1995) Four adult patients with the missense mutation L206W and a mild cystic fibrosis phenotype. Login to comment