Analysis of CNVs of <i>CFTR</i> gene in Chinese Han population with CBAVD

Ma, Chengquan; Wang, Ruyi; Li, Tengyan; Li, Hongjun; Wang, Binbin

doi:10.1002/mgg3.1506

Cited by 9 publications

(6 citation statements)

References 32 publications

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“…The majority of patients with CAVD carried at least one mutation, but only 11.11% of them carried more than one mutations. This result is similar to other studies in Chinese men (Jiang et al, 2014;Ma et al, 2020;Yang et al, 2020).…”

Section: Discussionsupporting

confidence: 93%

Mutations in CFTR genes are associated with oligoasthenospermia in infertile men undergoing IVF

Li¹,

Yan²,

Zhao³

et al. 2021

Andrologia

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It has been widely accepted that CAVD has a common genetic origin with cystic fibrosis. CAVD is considered as an atypical form of cystic fibrosis, leading to male infertility due to azoospermia (Bieth et al., 2021). Different mutations or variations in the CFTR gene were confirmed to be related to a wide spectrum of clinical phenotypes (Yang et al., 2015;Yuan et al., 2019). According to the Cystic Fibrosis Mutation Database (http://www.genet.sickk ids.on.ca/Home.html), 2104 mutations have been reported currently, including 27 exons and 26 introns. CFTR gene mutations exhibit striking genetic and epigenetic discrepancies in CAVD patients, whilst the most common mutation reported in Caucasians such as F508del is rarely seen in Chinese. Instead, the milder mutation as 5T is reported with higher

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Section: Discussionsupporting

confidence: 93%

Mutations in CFTR genes are associated with oligoasthenospermia in infertile men undergoing IVF

Li¹,

Yan²,

Zhao³

et al. 2021

Andrologia

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“…Our top 3 common mutations (exon 16-17b deletion; c.1322T>C, p.Leu441Pro; c.3871C>T, p.Gln1291Ter) were mostly restricted to Asian patients. 17 30 31 We observed sufficient L441P-CFTR L441P-CFTR correction by VX809 and VX661. 17 Our findings indicate that CFTR modulators can functionally improve CFTR channels in patients with the p.Leu441Pro mutation.…”

Section: Discussionmentioning

confidence: 75%

Multicenter Surveillance of Cystic Fibrosis in Korean Children

Kim

Hong

Ahn

et al. 2022

Allergy Asthma Immunol Res

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Purpose Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene, is rare among non-Caucasians. We aimed to identify the clinical features and CFTR mutations in Korean children. Methods We included 18 pediatric patients with CF diagnosed using sweat chloride test or genetic analysis for 30 years. HEK293 cells were transfected with wild-type CFTR , ΔF508- CFTR , and L441P- CFTR mutant plasmids for 24 hours and treated with CFTR correctors (VX809 and VX661). Results The median age at diagnosis was 9.2 years. Eleven patients had growth retardation, and 6 had a respiratory failure at diagnosis. Genetic analysis was used for all patients, while sweat testing was for 8 patients. At diagnosis, the median z scores of forced expiratory volume in one second (FEV1), FEV1/forced vital capacity, and forced expiratory flow at 25%–75% of forced vital capacity were −3.61 (−5.78, 1.78), −3.38 (−4.40, −0.60), and −4.45 (−5.78, 0.54), respectively. Two patients were treated with dornase alfa and only one with CFTR modulator. Patients were followed up for 3.7 years as a median. Four patients died at 10.6 years, with 4.2 years of post-diagnosis survival. The most common mutation was exon 16-17b deletion (19.4%). Among 11 single nucleotide variants, c.1322T>C (p.Leu441Pro, L441P) was detected in 4 patients. In the functional assay, L441P-CFTR correction was well restored by CFTR correctors compared with ΔF508. Conclusions CF is extremely rare in Korean children and is caused by different mutations from those commonly observed in Caucasians. Early diagnosis and treatment availability may improve outcomes. CFTR modulators may be effective for Asian patients with rare CFTR mutations, c.1322T>C (p.Leu441Pro).

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“…Therefore, the role of this mutation in azoospermia requires confirmation in a larger patient cohort. Recent research reported that among 263 Chinese patients with CBAVD, 5 (1.9%) patients were detected for copy number variants in the region of the CFTR gene (four of them carried partial deletions and one carried partial duplication of CFTR ), 37 but other studies did not find copy number variations of CFTR in males with CBAVD. 38 , 39 A larger number of samples and more sensitive gene detection methods are essential for further research.…”

Section: Discussionmentioning

confidence: 95%

Loss-of-function CFTR p.G970D missense mutation might cause congenital bilateral absence of the vas deferens and be associated with impaired spermatogenesis

Hou

Wang

et al. 2022

Asian Journal of Andrology

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Congenital bilateral absence of the vas deferens (CBAVD) is observed in 1%–2% of males presenting with infertility and is clearly associated with cystic fibrosis transmembrane conductance regulator ( CFTR ) mutations. CFTR is one of the most well-known genes related to male fertility. The frequency of CFTR mutations or impaired CFTR expression is increased in men with nonobstructive azoospermia (NOA). CFTR mutations are highly polymorphic and have established ethnic specificity. Compared with F508Del in Caucasians, the p.G970D mutation is reported to be the most frequent CFTR mutation in Chinese patients with cystic fibrosis. However, whether p.G970D participates in male infertility remains unknown. Herein, a loss-of-function CFTR p.G970D missense mutation was identified in a patient with CBAVD and NOA. Subsequent retrospective analysis of 122 Chinese patients with CBAVD showed that the mutation is a common pathogenic mutation (4.1%, 5/122), excluding polymorphic sites. Furthermore, we generated model cell lines derived from mouse testes harboring the homozygous Cftr p.G965D mutation equivalent to the CFTR variant in patients. The Cftr p.G965D mutation may be lethal in spermatogonial stem cells and spermatogonia and affect the proliferation of spermatocytes and Sertoli cells. In spermatocyte GC-2(spd)ts (GC2) Cftr p.G965D cells, RNA splicing variants were detected and CFTR expression decreased, which may contribute to the phenotypes associated with impaired spermatogenesis. Thus, this study indicated that the CFTR p.G970D missense mutation might be a pathogenic mutation for CBAVD in Chinese males and associated with impaired spermatogenesis by affecting the proliferation of germ cells.

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Analysis of CNVs of CFTR gene in Chinese Han population with CBAVD

Cited by 9 publications

References 32 publications

Mutations in CFTR genes are associated with oligoasthenospermia in infertile men undergoing IVF

Mutations in CFTR genes are associated with oligoasthenospermia in infertile men undergoing IVF

Multicenter Surveillance of Cystic Fibrosis in Korean Children

Loss-of-function CFTR p.G970D missense mutation might cause congenital bilateral absence of the vas deferens and be associated with impaired spermatogenesis

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