ABCMdb

PMID: 16128988

Larriba S, Bonache S, Sarquella J, Ramos MD, Gimenez J, Bassas L, Casals T
Molecular evaluation of CFTR sequence variants in male infertility of testicular origin.
Int J Androl. 2005 Oct;28(5):284-90., [PubMed]

Sentences

No. Mutations Sentence Comment

51 ABCC7 p.Arg117His ABCC7 p.Arg334Trp ABCC7 p.Asp1270Asn ABCC7 p.Ile148Thr ABCC7 p.Arg75Gln ABCC7 p.Ser1235Arg ABCC7 p.Met348Lys ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Pro111Leu ABCC7 p.Ser1426Phe CFTR analysis We identified 14 different, potential disease-causing CFTR sequence variants, 11 of them are translated into missense amino acid changes (p.R75Q, p.P111L, p.R117H, p.I148T, p.R334W, p.M348K, p.G576A, p.R668C, p.D1270N, p.S1235R and p.S1426F), one deletion (p.F508del) and two alleles affecting exon splicing [IVS8-6(5T), c.1716G>A] in 30 of 83 infertile patients (Table 1) giving a frequency of 36.1%. Login to comment 53 ABCC7 p.Val754Met ABCC7 p.Ile148Thr ABCC7 p.Arg75Gln ABCC7 p.Ser1235Arg ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Leu997Phe ABCC7 p.Asp836Tyr ABCC7 p.Glu725Lys ABCC7 p.Thr351Ser Thirteen CFTR gene sequence variants [p.R75Q, p.I148T, p.T351S, p.F508del, p.G576A, p.R668C, p.E725K, p.V754M, p.D836Y, p.L997F, p.S1235R, IVS8-6(5T) and c.1716G>A] were determined in 11 F1 and 15 F2 individuals (Table 1) giving a frequency of 29.9%. Login to comment 54 ABCC7 p.Ile148Thr ABCC7 p.Arg75Gln One individual presented both p.R75Q and p.I148T. Login to comment 72 ABCC7 p.Arg117His ABCC7 p.Arg334Trp ABCC7 p.Asp1270Asn ABCC7 p.Ile148Thr ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Ser1235Arg ABCC7 p.Ser1235Arg ABCC7 p.Met348Lys ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Gly576Ala ABCC7 p.Gly576Ala ABCC7 p.Gly576Ala ABCC7 p.Pro111Leu ABCC7 p.Asp836Tyr Description of genetic abnormalities and other risk factors of infertile and fertile CFTR carrier individuals No. Phenotype CFTR genotype Associated factors Testicular histologya b c Infertile individuals 1 NOb (SO) p.R75Q No Severe hypospermatogenesis 2 NOb (SO) p.R75Q No nd 3 NOb (A) p.P111L AZFb,c del Sertoli cell only 4 NOb (A) p.R117H AZFc del Severe hypospermatogenesis 5 NOb (SO) p.I148T No Severe hypospermatogenesis 6 NOb (A) p.R334W No Primary spermatocyte arrest 7 NOb (SO) p.M348K UV grade III Primary spermatocyte arrest 8 NOb (A) p.F508del No Sertoli cell only 9 NOb (A) p.F508del No Primary spermatocyte arrest 10 NOb (A) p.G576A, p.R668C No Severe hypospermatogenesis, Leydig cell hyperplasia 11 NOb (SO) p.G576A, p.R668C No Primary spermatocyte arrest (unilateral) 12 NOb (SO) p.G576A, p.R668C No Severe hypospermatogenesis 13 NOb (A) p.R668C UC Sertoli cell-only (incomplete) 14 NOb (SO) p.D1270N No nd 15 NOb (SO) p.S1235R No Severe hypospermatogenesis 16 NOb (SO) p.S1426F* UC Sertoli cell only 17 NOb (A) (T)5-(TG)12 No Severe hypospermatogenesis, Sertoli cell only (80%) 18 NOb (A) (T)5-(TG)12 No Sertoli cell only 19 NOb (SO) (T)5-(TG)11 UV grade III Bilateral moderate hypospermatogenesis 20 NOb (SO) (T)5-(TG)11 UV grade II Severe hypospermatogenesis 21 NOb (A) (T)5-(TG)11 No nd 22 NOb (SO) c.1716 G>A Dysplasia SV Severe hypospermatogenesis, Sertoli cell only (95%) 23 NOb (A) c.1716 G>A No nd 24 NOb (A) c.1716 G>A No Primary spermatocyte arrest (bilateral) 25 NOb (SO) c.1716 G>A No Sertoli cell only (95%) 26 NOb (SO) c.1716 G>A No Severe hypospermatogenesis 27 NOb (SO) c.1716 G>A UV grade III Severe hypospermatogenesis 28 NOb (SO) c.1716 G>A No nd 29 NOb (SO) c.1716 G>A No nd 30 NOb (SO) c.1716 G>A AZFc del Severe hypospermatogenesis Fertile individuals 1 F1 p.R75Q No nd 2 F1 p.F508del No nd 3 F1 p.F508del No nd 4 F1 p.G576A, p.R668C/ c.1716 G>A No nd 5 F1 p.D836Y No nd 6 F1 p.S1235R/c.1716 G>A No nd 7 F1 c.1716 G>A No nd 8 F1 c.1716 G>A No nd 9 F1 c.1716 G>A No nd 10 F1 c.1716 G>A No nd 11 F1 c.1716 G>A No nd 12 F2 p.R75Q No nd the expected CF carrier frequency in the local population (Van der Ven et al., 1996; Larriba et al., 2001; Dohle et al., 2002) or with the general population (Jakubiczka et al., 1999; Pallares-Ruiz et al., 1999; Ravnik-Glavac et al., 2001) and not normospermic fertile individuals, the latter considered as adequate controls. Login to comment 77 ABCC7 p.Arg117His ABCC7 p.Arg334Trp ABCC7 p.Ile148Thr Most of the changes identified, except p.F508del, p.R117H, p.I148T and p.R334W, are known to behave as benign mutations being present in milder phenotypes of CFTR-related pathologies (http:// www.genet.sickkids.on.ca) and/or because of the results of the performance of functional studies. Login to comment 78 ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala Some variants affect normal mRNA splicing leading to skipping of exon 9 [IVS8-6(5T) (Chu et al., 1993)], exon 10 [c.1716G>A (p.E528E) (Dork et al., 1997)] and exon 12 [p.G576A and p.R668C (Pagani et al., 2003]. Login to comment 79 ABCC7 p.Ser1426Phe p.S1426F (c.4409 C>T) in exon 24 represents a novel mutation described here for the first time. Login to comment 85 ABCC7 p.Val754Met ABCC7 p.Ile148Thr ABCC7 p.Arg75Gln ABCC7 p.Leu997Phe ABCC7 p.Glu725Lys ABCC7 p.Thr351Ser Continued No. Phenotype CFTR genotype Associated factors Testicular histologya b c 13 F2 p.I148T p.R75Q No nd 14 F2 p.T351S No nd 15 F2 p.F508del No nd 16 F2 p.E725K No nd 17 F2 p.V754M No nd 18 F2 p.L997F No nd 19 F2 (T)5-(TG)12 No nd 20 F2 (T)5-(TG)12 No nd 21 F2 (T)5-(TG)11 No nd 22 F2 (T)5-(TG)11 No nd 23 F2 c.1716 G>A No nd 24 F2 c.1716 G>A No nd 25 F2 c.1716 G>A No nd 26 F2 c.1716 G>A No nd Phenotype: NOb (SO), non-obstructive severe oligozoospermia; NOb (A), non-obstructive azoospermia; F1, optimal fertility; F2, suboptimal fertility. Login to comment