Complete mutational screening of the cystic fibrosis transmembrane conductance regulator gene: cystic fibrosis mutations are not involved in healthy men with reduced sperm quality

Pallares-Ruiz, Nathalie; Carles, Soukeyna; Georges, Marie des; Guittard, Caroline; Arnal, F.; Humeau, C; Claustres, Mireille

doi:10.1093/humrep/14.12.3035

Cited by 39 publications

(31 citation statements)

References 21 publications

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“…29 Thus, although a particular allele by itself might have no deleterious consequences, the combination of specific alleles at several polymorphic loci might lead to less functional or even insufficient CFTR protein. 15,30 In conclusion, this study indicates that the 5T allele in intron 8 of CFTR or IVS8-5T linked to either 12 or 13 TG repeats exhibit a high prevalence among the CBAVD patients tested. Moreover, a statistically significant relationship between the TG12-5T-V470 haplotype and CBAVD was detected for the Chinese population.…”

Section: Cftr Polymorphisms In Chinese Males With Cbavd Wh Ni Et Al 688mentioning

confidence: 58%

The CFTR polymorphisms poly-T, TG-repeats and M470V in Chinese males with congenital bilateral absence of the vas deferens

Ni¹,

Jiang²,

Fei³

et al. 2012

Asian J Androl

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Congenital bilateral absence of the vas deferens (CBAVD) is a frequent cause of obstructive azoospermia, and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene have also been frequently identified in patients with CBAVD. However, the distribution of the CFTR polymorphisms M470V, poly-T, TG-repeats and F508del mutation in the Chinese CBAVD population with presumed low cystic fibrosis (CF) frequency remains to be evaluated. Samples obtained from 109 Chinese infertile males with CBAVD and 104 normal controls were analyzed for the presence of CFTR (TG)m(T)n, M470V and F508del by PCR amplification followed by direct sequencing. Our study showed that the F508del mutation was not found in our patients. The 5T mutation was present with high frequency in Chinese CBAVD patients and IVS8-5T linked to either 12 or 13 TG repeats was highly prevalent among CBAVD patients (97.22% of 72 cases and 96.91% of 97 alleles with IVS8-5T). Moreover, a statistically significant relationship between TG12-5T-V470 haplotype and CBAVD was detected. This study indicated that the CFTR polymorphisms poly-T, TG-repeats and M470V might affect the process of CBAVD in the Chinese population.

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Section: Cftr Polymorphisms In Chinese Males With Cbavd Wh Ni Et Al 688mentioning

confidence: 58%

The CFTR polymorphisms poly-T, TG-repeats and M470V in Chinese males with congenital bilateral absence of the vas deferens

Ni¹,

Jiang²,

Fei³

et al. 2012

Asian J Androl

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“…This was higher than in Vietnamese (41%) [14] and Japanese (51%-54%) [14,15] , but lower than in Caucasians (67%) [14] . The main dominant haplotypes were (TG)11 and (TG)12 in the Chinese population, as well as other Asian populations, however, in Caucasians, after the (TG)11 haplotype, the most common was the (TG)10 haplotype [14,25] . As previously reported, the TG-repeats that join with poly-T tracts also influence splicing of exon 9 [12] , and when present on the same allele as a T5 tract, the longer the TG-repeats, the higher the proportion of CFTR transcripts that will lack exon 9.…”

Section: Discussionmentioning

confidence: 88%

“…Conversely, T7-TG12-M470V was the main haplotype in Vietnamese. However, in Caucasians, two main haplotypes, T7-(TG)11-V470 and T7-(TG)10-M470 are predominant [14,25] . As previously reported, TG-repeats also influence the function of CTFR protein, and longer TG repeats increase the proportion of CFTR transcripts that lack exon 9 [12] .…”

Section: Discussionmentioning

confidence: 97%

Comparative analysis of common CFTR polymorphisms poly-T, TG-repeats and M470V in a healthy Chinese population

Qin¹,

Ding²,

Wei³

2008

WJG

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Huang Q, Ding W, Wei MX. Comparative analysis of common CFTR polymorphisms poly-T, TG-repeats and M470V in a healthy Chinese population. World J Gastroenterol 2008; 14(12): 1925-1930 INTRODUCTIONThe cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7q31 spans approximately 250 kb of DNA and encodes 27 exons encodes [1] . The CFTR gene encodes a cAMP-and ATP-dependent chloride channel that is present in the apical membrane of the epithelial cells that line most exocrine glands [2] . Phosphorylation of the regulatory domain by protein kinase A, followed by binding and hydrolysis of ATP at both nucleotide-binding domains, regulates the transport of chloride ions through the channel [3] . Absence, reduced levels, or malfunction of the CFTR protein results in cystic fibrosis (CF), and CF-like diseases such as congenital bilateral absence of the vas deferens (CBAVD) [4,5] , bronchiectasis [6] and chronic pancreatitis [7] . Since the discovery of the CFTR gene, more than 1000 mutations and 200 polymorphisms have been identified [8] . CF is one of the most common autosomal recessive disorders in Caucasians, with an incidence of approximately 1 in 2500 Caucasian births and a carrier frequency of approximately 1 in 25. However, in Asians, the prevalence of CF is very low, with an incidence of approximately 1 in 100 000, and in particular, the severe mutations, such as ∆F508, G542X and N1303K, are rarely found in Asians. Previous studies have demonstrated that polymorphisms outside the CFTR gene [9,10] , as well as within the gene, may affect transcription or function of the CFTR protein and modify the phenotype of some CF mutations. It has been mentioned that poly-T, TG-repeats and M470V polymorphisms play a role in the development of CF-like diseases. The poly-T tract located at the junction of intron Abstract AIM: To investigate the three important cystic fibrosis transmembrane conductance regulator (CFTR ) haplotypes poly-T, TG-repeats and the M470V polymorphisms in the Chinese population, and to compare their distribution with that in Caucasians and other Asian populations. RAPID COMMUNICATION METHODS:Genomic DNA was extracted from blood leukocytes. Exons 9 and 10 of the CFTR gene were obtained through polymerase chain reaction (PCR). Exon 9 DNA sequences were directly detected by an automated sequencer and poly-T and TG-repeats were identified by direct sequence analysis. Pure exon 10 PCRamplified products were digested by Hph Ⅰ restriction enzyme and the M470V mutation was detected by the AGE photos of digestion products.RESULTS: T7 was the most common (93.6%) haplotype and the (TG)11 frequency of 57.2% and (TG)12 frequency of 40.9% were dominant haplotypes in the junction of intron 8 (IVS-8) and exon 9. The frequency of T5 was 3.8% and all T5 allele tracts (10 alleles) were joined with (TG)12. Four new alleles of T6 (1.5%) were found in three healthy individuals. In exon 10, the V allele (56.1%) was slightly more frequent than the M allele (43.9%), and the M/V (45.5%) was the dominan...

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“…An increased prevalence of CFTR mutations in male subjects with nonobstructive infertility has been reported in previous studies, 22,23 but this association has not been invariably confirmed. 18,24,25 Thus, the relation between CFTR mutations and male infertility requires further assessment. The prevalence of the 5T polymorphism in the total series of analyzed individuals (6.5%) was not different from the expected (5 -10%), but again a significant difference was found within different couples' subgroups.…”

Section: Discussionmentioning

confidence: 99%

Screening of mutations in the CFTR gene in 1195 couples entering assisted reproduction technique programs

et al. 2005

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Genetic testing of the cystic fibrosis transmembrane conductance ( CFTR) gene is currently performed in couples undergoing assisted reproduction techniques ( ART), because of the high prevalence of healthy carriers in the population and the pathogenic relationship with congenital bilateral absence of vas deferens ( CBAVD). However, discordant data have been reported concerning the usefulness of this genetic test in couples with no family history of cystic fibrosis ( CF). In this study, we report the results of CFTR molecular screening in 1195 couples entering ART. Genetic testing was initially carried out in a single partner of each couple. CFTR mutations were detected in 55 subjects ( 4.6%), a percentage that overlaps with the one reported in the general population. However, significantly higher frequencies of were found in CBAVD individuals ( 37.5%) and in males with nonobstructive azoospermia ( 6.6%). The 5T allele was found in 78 patients ( 6.5%). This figure was again significantly different in males with nonobstructive-azoospermia ( 9.9%) and in those with CBAVD ( 100%). All together, 139 subjects ( 11.6%) had either a CFTR mutation or the 5T allele. Subsequent molecular analysis of their partners disclosed a CFTR mutation or 5T allele in nine cases ( 6.5%). However, none of these couples had CFTR alterations in both members, a CFTR mutation being invariably present in one partner and the 5T allele in the other. In order to improve genetic counselling of these couples, the TG-M470V-5T association was analyzed, and a statistically significant relationship between 12TG-V470 and CBAVD was detected

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Complete mutational screening of the cystic fibrosis transmembrane conductance regulator gene: cystic fibrosis mutations are not involved in healthy men with reduced sperm quality

Cited by 39 publications

References 21 publications

The CFTR polymorphisms poly-T, TG-repeats and M470V in Chinese males with congenital bilateral absence of the vas deferens

The CFTR polymorphisms poly-T, TG-repeats and M470V in Chinese males with congenital bilateral absence of the vas deferens

Comparative analysis of common CFTR polymorphisms poly-T, TG-repeats and M470V in a healthy Chinese population

Screening of mutations in the CFTR gene in 1195 couples entering assisted reproduction technique programs

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