Heterogeneity for mutations in the CFTR gene and clinical correlations in patients with congenital absence of the vas deferens

Casals, Teresa; Bassas, Lluís; Egozcue, Susanna; Ramos, María Dolores Burguete; Giménez, Joaquím; Segura, Ana; García, F. Baranda; Carrera, Marta; Larriba, Sara; Sarquella, Joaquim; Estivill, Xavier

doi:10.1093/humrep/15.7.1476

Cited by 130 publications

(131 citation statements)

References 34 publications

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“…In the 17 CBAVD patients of our sample, we detected seven different mutations, including the 5T variant. This variant was found at a frequency of 23.5%, which is in accordance with previous reports , Casals et al, 2000, thus confirming its association with CBAVD. The ∆F508 deletion was found on five chromosomes and was the second most frequent mutation.…”

Section: Discussionsupporting

confidence: 92%

“…No alterations were found in seven patients with CBAVD and in the three azoospermic patients without CBAVD. A high number of different CFTR mutations have been reported in patients with CBAVD Dörk et al, 1997;Mak et al, 1999;Casals et al, 2000). Most of these mutations correspond to amino acid changes or splice site mutations, and they are likely to cause a mild CF phenotype (Casals et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

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Analysis of mutations in the cystic fibrosis transmembrane regulator (CFTR) gene in patients with obstructive azoospermia

2003

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Congenital bilateral absence of the vas deferens (CBAVD) accounts for 1%-2% of sterility in men. A high incidence of mutations, as well as the involvement of the 5T variant of the T tract length in intron 8 of the cystic fibrosis conductance regulator (CFTR) gene, have been previously described in males with CBAVD. Herein we report the screening for mutations and for the 5T variant of the CFTR gene in 17 patients with CBAVD and three others with non-CABVD obstructive azoospermia. In the CBAVD group, three patients (15%) were compound heterozygotes for mutations, and five patients (25%) had a mutation in one allele and the 5T variant in the other; the 5T variant was also present in two other patients, one of them being homozygous. The most frequent mutation was ∆F508, present on five chromosomes (12.5%). A novel missense mutation (A399D) was detected in a Japanese CBVAD patient. Our results yield further evidence for a strong association between male obstructive azoospermia caused by CBAVD and mutation/5T variant in the CFTR gene. The search for CFTR mutations in such patients is thus recommended for genetic counseling of couples who undergo assisted fertilization due to CBAVD.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Analysis of mutations in the cystic fibrosis transmembrane regulator (CFTR) gene in patients with obstructive azoospermia

2003

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“…This finding suggests the presence of a mixed pathology, with both obstructive damage and testicular failure. In agreement with the literature data (Schlegel Casals et al, 2000;Daudin et al, 2000;Dohle, 2010), around 20% of the men in our series had a history of genital anomalies. That might be one explanation for why some patients do indeed show signs of non-obstructive azoospermia.…”

Section: Discussionsupporting

confidence: 93%

Congenital bilateral absence of the vas deferens: the impact of spermatogenesis quality on intracytoplasmic sperm injection outcomes in 108 men

et al. 2015

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SUMMARYIn azoospermic men with congenital bilateral absence of the vas deferens (CBAVD), it is not known whether the outcomes of intracytoplasmic sperm injection (ICSI) depend on the quality of testicular spermatogenesis (as determined histopathologically). We retrospectively studied the impact of spermatogenesis quality on ICSI outcomes in 108 azoospermic men with CBAVD consulting in a university hospital's department of andrology and reproductive biology. As part of an ICSI program, sperm samples were obtained from the epididymis [by microsurgical epididymal sperm aspiration (MESA); n = 47] or the testis [by testicular sperm extraction (TESE); n = 14] or both (MESA + TESE, n = 47). In the TESE group (i.e., TESE-only and MESA + TESE), spermatogenesis was normal in 21 of the 108 men (19.4%) and hypospermatogenesis occurred in 33 (30.5%). The fertilization rate was significantly lower in the hypospermatogenic group than in the normospermatogenesis group (65.6 and 72.9%, respectively; p = 0.02); this was also true for the embryo cleavage rate (88.6 and 92.1%, respectively; p = 0.007), and the proportion of embryos with fewer than 30% of enucleate fragments (79.5 and 86.9%, respectively; p = 0.02). Our study results showed that impaired spermatogenesis had a negative impact on certain early-stage biological outcomes of ICSI. In CBAVD, male factors are likely to exert a harmful effect on the early stages of embryo development.

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“…11,48,49 Additional data should be provided to determine the utility of CFTR testing in these situations.…”

Section: Indications For Cftr Testingmentioning

confidence: 99%

Best practice guidelines for molecular genetic diagnosis of cystic fibrosis and CFTR-related disorders – updated European recommendations

Dequeker

Stuhrmann

Morris³

et al. 2008

Eur J Hum Genet

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208

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The increasing number of laboratories offering molecular genetic analysis of the CFTR gene and the growing use of commercial kits strengthen the need for an update of previous best practice guidelines (published in 2000). The importance of organizing regional or national laboratory networks, to provide both primary and comprehensive CFTR mutation screening, is stressed. Current guidelines focus on strategies for dealing with increasingly complex situations of CFTR testing. Diagnostic flow charts now include testing in CFTR-related disorders and in fetal bowel anomalies. Emphasis is also placed on the need to consider ethnic or geographic origins of patients and individuals, on basic principles of risk calculation and on the importance of providing accurate laboratory reports. Finally, classification of CFTR mutations is reviewed, with regard to their relevance to pathogenicity and to genetic counselling.

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Heterogeneity for mutations in the CFTR gene and clinical correlations in patients with congenital absence of the vas deferens

Cited by 130 publications

References 34 publications

Analysis of mutations in the cystic fibrosis transmembrane regulator (CFTR) gene in patients with obstructive azoospermia

Analysis of mutations in the cystic fibrosis transmembrane regulator (CFTR) gene in patients with obstructive azoospermia

Congenital bilateral absence of the vas deferens: the impact of spermatogenesis quality on intracytoplasmic sperm injection outcomes in 108 men

Best practice guidelines for molecular genetic diagnosis of cystic fibrosis and CFTR-related disorders – updated European recommendations

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