ABCMdb

PMID: 10601093

Pallares-Ruiz N, Carles S, Des Georges M, Guittard C, Arnal F, Humeau C, Claustres M
Complete mutational screening of the cystic fibrosis transmembrane conductance regulator gene: cystic fibrosis mutations are not involved in healthy men with reduced sperm quality.
Hum Reprod. 1999 Dec;14(12):3035-40., [PubMed]

Sentences

No. Mutations Sentence Comment

22 ABCC7 p.Asp1152His As it has been shown recently (Cuppens et al.,CF` mutation on a gene and a 'mild` mutation retaining some residual CFTR activity on the other gene, such as the '5T 1998a) that some of the more common polymorphisms in the (c) European Society of Human Reproduction and Embryology CFTR gene affect expression and function of the CFTR protein, although only mutation D1152H is commonly accepted as a we also analysed the distribution of three intragenic markers disease-causing mutation and has been demonstrated to reduce [TGn and Tn in intron 8, and 1540A/G (M470V) in exon 10] chloride currents in vitro (Vankeerberghen et al., 1998). Login to comment 24 ABCC7 p.Met952Ile ABCC7 p.Phe1052Val The main objective of this F1052V (Mercier et al., 1993) and M952I (Girodon et al., study was to compare the complete CFTR genotypes of 56 1996) have been previously reported in CF and CBAVD men with OAT and 50 controls from the same population patients to the CF Genetics Analysis Consortium (CFGAC, background, in order to evaluate a putative involvement of http://www.genet.sickkids.on.ca/CFTR). Login to comment 25 ABCC7 p.Ile1230Thr I1230T, reported here CFTR severe or mild mutants and/or variants in infertility due for the first time, results from the nucleotide change 3821T/C to altered spermatogenesis. Login to comment 31 ABCC7 p.Ile1230Thr Theinformed consent for DNA studies, blood samples were collected change I1230T has not been detected in 960 CF and 300between May and August 1998. Login to comment 37 ABCC7 p.Val562Leu ABCC7 p.Gly622Asp G622D has been reported previously (Zielenski approved by the Clinical Research Committee of the University et al., 1996) in a patient with oligozoospermia, and V562L Hospital Montpellier. Login to comment 45 ABCC7 p.Phe508Cys Six variants present on using an improved procedure derived from a previously described OAT alleles, 1655T/G (F508C), 1716G/A (E528E), 2377C/T method (Chillon et al., 1995). Login to comment 48 ABCC7 p.Leu1096Arg 17b is a novel sequence change identified in only one subject from the general population, that changes a non-polar (leucine)Statistical analysis for a positively charged (arginine) amino acid residue (L1096R)χ2 test was used to compare differences between proportions. Login to comment 56 ABCC7 p.Asp1152His ABCC7 p.Met952Ile ABCC7 p.Phe1052Val ABCC7 p.Ile1230Thr ABCC7 p.Val562Leu ABCC7 p.Gly622Asp Four OAT men had a missense mutation on one chromosome, 1540 (M470V) in exon 10 was significantly different between Table I. Characterization of CFTR genotypes in 56 patients with oligoasthenoteratozoospermia (OAT) and in 50 controls Mutations IVS8(T)n 1540A/G Other variations IVS8(TG)n OAT 1 I1230T 7/7 A/G 1655T/G 12/12 1 D1152H 7/7 G/G - 11/11 1 F1052V 7/7 A/A 875ϩ40A/G 10/10 1 M952I 7/7 G/G 4404C/T 11/11 1 - 7/7 G/G 4404C/T 11/11 2 - 7/7 A/G 875ϩ40A/G 10/11 2 - 7/7 A/G 125G/C 11/12 1 - 7/7 A/A 125G/C 12/12 1 - 7/9 A/A 1716G/A, 3041-71G/C ϩ 4002A/Ga 11/10 1 - 7/7 G/G 356G/A, 405ϩ46G/T, 4374ϩ13A/G 11/11 1 - 7/7 A/A 875ϩ40A/G, 3499ϩ37G/A 10/10 1 - 7/9 A/A 1859G/C ϩ 2134C/Ta 10/10 1 - 7/7 A/G 4002A/G 12/12 1 - 7/9 A/G 4002A/G 11/10 1 - 7/7 G/G 2377C/T 11/11 1 - 7/7 A/A 875ϩ40A/G, 1716G/A 10/10 1 - 7/7 G/G 3417A/T 11/11 1 - 7/7 A/G 3417A/T 11/12 24 - 7/7 G/G - 11/11 2 - 7/9 A/G - 10/12 3 - 7/9 A/G - 11/10 2 - 7/9 A/A - 10/10 1 - 9/9 A/A - 10/10 2 - 7/7 A/G - 10/11 1 - 7/7 A/A - 10/10 1 - 7/7 G/G - 8/11 Controls 1 ∆F508 7/9 A/G - 10/12 1 ∆F508 7/9 A/A 875ϩ40A/G 10/11 1 V562L 7/7 A/A 223C/T 10/10 1 G622D 7/9 A/G 3041-71G/C ϩ 4002A/Ga 10/11 1 - 7/7 A/A 3419T/G 10/11 1 - 7/7 G/G 4002A/G 11/11 3 - 7/7 A/G 125G/C 11/11 1 - 7/7 G/G 125G/C 11/11 1 - 7/7 A/A 125G/C 10/11 1 - 7/7 A/A 125G/C 11/12 2 - 7/5 A/G 875ϩ40A/G 11/11 1 - 7/7 A/G 875ϩ40A/G 10/10 1 - 7/7 A/A 875ϩ40A/G, 125G/C 10/11 1 - 7/7 G/G 356G/A 11/11 1 - 7/7 A/G 356G/A 10/10 1 - 9/9 A/A 3041-71G/C ϩ 4002A/Ga 10/10 1 - 7/7 G/G 406-6T/C 11/11 1 - 7/7 A/G 3417A/T 10/11 1 - 7/7 G/G 4404C/T 11/11 1 - 7/7 A/G 1859G/Cϩ2134C/Ta 10/11 11 - 7/7 G/G - 11/11 6 - 7/7 A/G - 10/10 2 - 7/7 A/G - 11/11 1 - 7/7 A/G - 10/11 5 - 7/9 A/G - 10/12 2 - 7/5 G/G - 10/11 aDouble mutant alleles, In bold: mutations or variations previously undescribed. Login to comment 63 ABCC7 p.Arg75Gln ABCC7 p.Phe508Cys ABCC7 p.Leu1096Arg ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Arg31Cys Frequency distribution of CFTR gene variants in populations from southern France infertile men with OAT and in controls (T)n-1540A/G-(TG)n Controls OAT PVariants Allele frequency, % of chromosomes (n ϭ 50) (n ϭ 56) Controls CBAVDa OAT 9/9 A/A 10/10 1 (2) 1 (2) NS(n ϭ 100) (n ϭ 100) (n ϭ 112) 7/9 A/A 10/12 1 0 11/10 0 1223C/T (R31C) 0.01 0 0 10/10 0 3356G/A (R75Q) 0.02 0.01 0.009 Total 1 (2) 4 (7) NS1655T/G (F508C) 0 0.01 0.009 7/9 A/G 11/10 2 41716 G/A (E528E) 0 0.01 0.018 10/12 5 21859G/C (G576A)ϩ2134C/T 0.01 0.04c 0.009 7 (14) 6 (11) NS(R668C)b 7/7 A/A 12/12 0 12377C/T (L749L) 0 0.01d 0.009 11/12 1 03417A/T (T1095T) 0.01 0 0.018 10/11 3 03419T/G (L1096R) 0.01 0 0 10/10 1 44002A/G (P1290P) 0.01 0 0.018 Total 5 (10) 5 (9) NS4404C/T (T1424T) 0.01 0.01 0.018 7/7 A/G 12/12 0 2125G/C (5ЈUTR) 0.07 0.01 0.027 11/12 0 3405ϩ46G/T 0 0 0.018 11/11 5 0406-6T/C 0.01 0 0 10/11 3 3875ϩ40A/G 0.05 0.06 0.045 10/10 8 03041-71G/Cϩ4002A/Gb 0.02 0.02 0.009 Total 16 (32) 8 (14) NS3499ϩ37G/A 0 0 0.009 7/7 G/G 11/11 16 (32) 31 (55) Ͻ 0.024374ϩ13A/G 0 0 0.009 8/11 0 1 Total 16 (32) 32 (57) 0.018aGroup of CBAVD patients whose genotypes had been previously analysed 7/5 A/G 11/11 2 (4) 0 -in our laboratory. Login to comment 65 ABCC7 p.Asp443Tyr cThree CBAVD alleles with 1859G/Cϩ2134C/T and mutation D443Y. Login to comment 66 ABCC7 p.Arg764* NS ϭ not significant.dOne CBAVD allele with 2377C/T and mutation R764X. Login to comment 75 ABCC7 p.Arg75Gln ABCC7 p.Phe508Cys ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Arg31Cys Several missense variations identified in this study (R31C, R75Q, F508C, G576A, R668C, or E528E) have previously Table IV. Login to comment 79 ABCC7 p.Arg668Cys G/G 18 (36) 31 (55) 9 (18) Second, some variants can been found on chromosomes carrying 'true` CFTR mutations (for instance, R668C onaP ϭ 0.008 for comparison with the CBAVD group. Login to comment 81 ABCC7 p.Asp443Tyr CBAVD alleles carrying D443Y). Login to comment 84 ABCC7 p.Phe508Cys (for instance F508C associated in trans with ∆F508 (Desgeorges et al., 1994). Login to comment 129 ABCC7 p.Phe508Cys Desgeorges, M., Kjelleberg, P., Demaille, J. et al. (1994) A healthy male with compound and double heterozygosities for ∆F508, F508C, and M470V in exon 10 of the cystic fibrosis gene. Login to comment 146 ABCC7 p.Phe508Cys Mol. Hum. Reprod., 3, 419-430. Meschede, D., Eigel, A., Horst, J. et al. (1993) Compound heterozygosity for the ∆F508 and F508C cystic fibrosis transmembrane conductance regulator (CFTR) mutations in a patient with congenital bilateral aplasia of the vas deferens. Am. J. Hum. Genet., 53, 292-293. Meschede, D., Dworniczak, B., Behre, H.M. et al. (1997) CFTR gene mutations in men with bilateral ejaculatory-duct obstruction and anomalies of the seminal vesicles. Login to comment