Meta-analyses of 4 CFTR variants associated with the risk of the congenital bilateral absence of the vas deferens

Xu, Xuting; Zheng, Jing; Liao, Qi; Zhu, Huiqing; Xie, Hongyan; Shi, Huijuan; Duan, Shiwei

doi:10.1186/2043-9113-4-11

Cited by 13 publications

(13 citation statements)

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“…Furthermore, in the Ashkenazi Jewish population c.3846G > A (legacy name W1282X) is the most common mutation found (48% frequency). The meta-analysis by Xu et al (2014) which specifically looked at F508del, 5T, and M470V, supports the above findings, concluding that there are significant associations between F508del and CBAVD ( P < 0.001, OR = 22.20, 95% CI = 7.49–65.79), 5T and CBAVD ( P < 0.001, OR = 8.35, 95% CI = 6.68–10.43).…”

Section: Summary Of Outcomes and Narrative Review As Related To The Esupporting

confidence: 68%

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The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance—challenges and future research opportunities

Barratt

Björndahl

Jonge

et al. 2017

Human Reproduction Update

356

227

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BACKGROUNDHerein, we describe the consensus guideline methodology, summarize the evidence-based recommendations we provided to the World Health Organization (WHO) for their consideration in the development of global guidance and present a narrative review of the diagnosis of male infertility as related to the eight prioritized (problem or population (P), intervention (I), comparison (C) and outcome(s) (O) (PICO)) questions. Additionally, we discuss the challenges and research gaps identified during the synthesis of this evidence.OBJECTIVE AND RATIONALEThe aim of this paper is to present an evidence-based approach for the diagnosis of male infertility as related to the eight prioritized PICO questions.SEARCH METHODSCollating the evidence to support providing recommendations involved a collaborative process as developed by WHO, namely: identification of priority questions and critical outcomes; retrieval of up-to-date evidence and existing guidelines; assessment and synthesis of the evidence; and the formulation of draft recommendations to be used for reaching consensus with a wide range of global stakeholders. For each draft recommendation the quality of the supporting evidence was then graded and assessed for consideration during a WHO consensus.OUTCOMESEvidence was synthesized and recommendations were drafted to address the diagnosis of male infertility specifically encompassing the following: What is the prevalence of male infertility and what proportion of infertility is attributable to the male? Is it necessary for all infertile men to undergo a thorough evaluation? What is the clinical (ART/non ART) value of traditional semen parameters? What key male lifestyle factors impact on fertility (focusing on obesity, heat and tobacco smoking)? Do supplementary oral antioxidants or herbal therapies significantly influence fertility outcomes for infertile men? What are the evidence-based criteria for genetic screening of infertile men? How does a history of neoplasia and related treatments in the male impact on (his and his partner's) reproductive health and fertility options? And lastly, what is the impact of varicocele on male fertility and does correction of varicocele improve semen parameters and/or fertility?WIDER IMPLICATIONSThis evidence synthesis analysis has been conducted in a manner to be considered for global applicability for the diagnosis of male infertility.

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Section: Summary Of Outcomes and Narrative Review As Related To The Esupporting

confidence: 68%

“…No Cochrane reviews were identified. The primary evidence was from studies by Yu et al (2012) , Xu et al (2014) and Lommatzsch and Aris (2009) , and practice statements from ASRM (2012b) , AUA (2011) and EAU ( Jungwirth et al , 2015 ).…”

Section: Summary Of Outcomes and Narrative Review As Related To The Ementioning

confidence: 99%

The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance—challenges and future research opportunities

Barratt

Björndahl

Jonge

et al. 2017

Human Reproduction Update

356

227

View full text Add to dashboard Cite

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“…The c.1210‐12T [5] variant has been known to be associated with different CFTR‐related disorders such as chronic pancreatitis, bronchiectasis, rhinosinusitis, aspergillosis, as well as CBAVD (Ferec & Cutting, ). A varied frequency of c.1210‐12[5] (IVS9‐5T) has been reported across different populations (Xu et al., ). Notably, we found the c.1210‐12T[5] allele to be significantly higher in the cohort of CBAVD men (39.4%) as compared to the healthy men.…”

Section: Discussionmentioning

confidence: 99%

The CFTR gene mild variants poly-T, TG repeats and M470V detection in Indian men with congenital bilateral absence of vas deferens

et al. 2017

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The aim of the study was to detect the frequency of the CFTR gene variants poly-T, TG repeats and c.1408A>G p.Met470Val (M470V) in Indian men with congenital bilateral absence of the vas deferens (CBAVD). Men diagnosed with CBAVD (n = 76), their female partners (n = 76) and healthy men from general population (n = 50) were recruited. Genomic DNA was isolated and the polymorphic regions of IVS9- c.1210-12T [5] and M470V were amplified using specific primers followed by Sanger's DNA sequencing. A statistically significant increase in the frequency of heterozygous IVS9- c.1210-12T [5] (39.4%) was observed in CBAVD men as compared to controls (14%). The allelic distribution of c.1210-12T [5], c.1210-12T [7] and c.1210-12T [9] in CBAVD men was 21%, 64.4% and 13% and that in healthy controls was 7%, 73% and 20% respectively. Longest TG repeat c.1210-34TG [13] was found in association with c.1210-12T [5] with an allelic frequency of 5.9% in CBAVD men. We found a significant association of c.1210-34TG [12]/c.1210-34TG [13] - c.1210-12[5] -V470 allele in CBAVD men. Twelve female partners harboured a heterozygous c.1210-12T [5] allele. The study emphasises the need to screen both partners for the polymorphisms M470V, poly-T, TG tract repeats in addition to population-specific known CFTR gene mutations.

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“…However, previous studies on association between CFTR variants and CBAVD are not always consistent. Incomplete penetrance is observed with the 5T polymorphism (Chillon et al ., ), while there is still disagreement on the pathogenic role of the M470 variant in CBAVD (Xu et al ., ). Nonetheless, until recently, CFTR was the only validated gene with mutations that cause the majority of CBAVD, leaving the genetic origin of the remaining 20% unknown (Wu et al ., ; Li et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Pathogenic role of ADGRG2 in CBAVD patients replicated in Chinese population

et al. 2017

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Congenital bilateral absence of the vas deferens (CBAVD) is an important cause of obstructive azoospermia and male infertility worldwide. Cystic fibrosis transmembrane conductance regulator (CFTR) mutations are the main pathogenic cause, although a proportion of cases are still unexplained. Recently, adhesion G protein-coupled receptor G2 (ADGRG2) gene, a novel pathogenic gene for CBAVD was identified. We did a single population replication study in Chinese CBAVD patients to replicate its role in CBAVD developing. In this study, we performed whole-exome sequencing in 18 unrelated CBAVD patients and identified two missense variants in two patients (c.G1709A, p.C570Y; and c.A2968G, p.K990E). Both variants were predicted to be deleterious and highly conserved in silico. The p.C570Y variant is located in the G protein-coupled receptor (GPCR) proteolysis site domain, which is functionally necessary for autoproteolysis, while the p.K990E variant is in the N-terminal fragment that may regulate activity of the adhesion GPCR. We did not find any potential pathogenic CFTR variants, implying the ADGRG2 variants are the genetic cause in these patients. To the best of our knowledge, these are the first two ADGRG2 variants to be identified in Chinese CBAVD patients, which further validate the disease-causing role of ADGRG2 in this congenital defect.

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Meta-analyses of 4 CFTR variants associated with the risk of the congenital bilateral absence of the vas deferens

Cited by 13 publications

References 30 publications

The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance—challenges and future research opportunities

The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance—challenges and future research opportunities

The CFTR gene mild variants poly-T, TG repeats and M470V detection in Indian men with congenital bilateral absence of vas deferens

Pathogenic role of ADGRG2 in CBAVD patients replicated in Chinese population

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