Genetic Diagnosis and Sperm Retrieval Outcomes for Chinese Patients with Congenital Bilateral Absence of Vas Deferens

In this study, we aimed to study the mutation spectrum ofCFTR andADGRG2 in a group of CBAVD patients and to evaluate sperm retrieval outcomes in a subset of CBAVD patients.Materials and methodsNext ‐generation targeted sequencing was used to identify mutations in theCFTR andADGRG2 genes in 38 CBAVD patients. In addition, we followed and analyzed nine of the 38 patients who were undergoing sperm retrieval surgery.ResultsIn total, 27 of 38 (71.05%) patients carried at least one likely pathogenic or pathogenic mutation inCFTR orADGRG2. In addition to the IVS9 ‐5T allele, 15CFTR and 1ADGRG2 mutations were identified, including 4 novel mutations.CFTR hot ‐spot mutations were not identified in our study. Sperm was successfully obtained in all nine patients who underwent MESA or TESE surgery, but most patients had sperm with relatively low motility and high abnormality rates.Discussion and conclusionExcept for the IVS9 ‐5T allele, hot‐spot mutations ofCFTR may not exist in Chinese CBAVD patients. Therefore, next ‐generation targeted sequencing for wholeCFTR andADGRG2 gene may be the appropriate genetic testing method, and genetic counseling may be different from Caucasian populations. We observed a high success rate of sperm retrieval with relatively low motility and high abnormality rates in Chinese CBAVD patients. However, this is only a weak conclusion due to the small sample size.
Source: Andrology - Category: Urology & Nephrology Authors: Tags: ORIGINAL ARTICLE Source Type: research

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Male factor infertility is an important clinical problem whose most severe phenotype, severe oligospermia or azoospermia, has a variety of genetic causes. Some, like Klinefelter syndrome or cystic fibrosis, are well understood, but most are still unknown, and Y chromosome microdeletions only explain a fraction of the remaining cases. In consanguineous and nonconsanguineous families, whole exome sequencing (WES) has been successfully used to identify likely causal mutations in severe oligospermia (1, 2).
Source: Fertility and Sterility - Category: Reproduction Medicine Authors: Tags: Reflections Source Type: research
AbstractCongenital absence of the vas deferens (CAVD) may have various clinical presentations depending on whether it is bilateral (CBAVD) or unilateral (CUAVD), complete or partial, and associated or not with other abnormalities of the male urogenital tract. CBAVD is usually discovered in adult men either during the systematic assessment of cystic fibrosis or otherCFTR-related conditions, or during the exploration of isolated infertility with obstructive azoospermia. The prevalence of CAVDs in men is reported to be approximately 0.1%. However, this figure is probably underestimated, because unilateral forms of CAVD in asy...
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research
ConclusionsOur results indicate that men with CUAVD mainly display oligozoospermia or normozoospermia and that they were previously fertile. They clearly confirm, first, thatCFTR testing is recommended in CUAVD men and it should be mandatory for those with normal kidneys; and, second, that TRUS is needed for the diagnosis of CUAVD. As CUAVD may be present whatever the sperm count, biological warnings are represented by semen volume and seminal epididymal markers, and clinical warnings by surgical histories of undescended testes or inguinal hernia.
Source: Andrology - Category: Urology & Nephrology Authors: Tags: ORIGINAL ARTICLE Source Type: research
ConclusionOur results confirm the interest ofADGRG2 sequencing in patients with CAVD not formerly related to CFTR dysfunction, especially in absence of associated unilateral renal agenesis.
Source: Andrology - Category: Urology & Nephrology Authors: Tags: ORIGINAL ARTICLE Source Type: research
ConclusionOur findings may broaden the mutation spectrum ofCFTR in CAVD patients and provide more familial evidence that the combination of a mild variant and a severe variant intrans ofCFTR can cause vas deferens malformation.
Source: Journal of Assisted Reproduction and Genetics - Category: Reproduction Medicine Source Type: research
This article reviews the pathophysiology, diagnosis, and management of infertility and testosterone deficiency that occur in men with CF. With improving survival of CF patients, these topics are becoming more significant in their clinical care.
Source: Journal of Cystic Fibrosis - Category: Respiratory Medicine Authors: Source Type: research
This study aim to explore the promoter region of CFTR gene in CBAVD patients and study the mutations by functional analysis, and to discuss the significance of mutation testing in this area. We performed screening analysis on 65 CBAVD patients and 50 controls to detect mutations in the CFTR gene, and studied the functions of promoter mutations using reporter gene constructs, transient transfection techniques and subsequent assessment of transcriptional activity and expression levels. Mutations c.-195C>A and c.-34C>T in the promoter region of the CFTR gene were detected in 4 of our Chinese CBAVD patients, one of which...
Source: Gene - Category: Genetics & Stem Cells Authors: Tags: Gene Source Type: research
AbstractAs with many other diseases, genetic testing in human azoospermia was initially restricted to karyotype analyses (leading to diagnostic chromosome rearrangement tests for Klinefelter and other syndromes). With the advent of molecular biology in the 1980s, genetic screening was broadened to analyses of Y chromosome microdeletions and the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). Decades later, the emergence of whole-genome techniques has led to the identification of other genetic defects associated with human azoospermia. AlthoughTEX11 andADGRG2 defects are frequently described ...
Source: Basic and Clinical Andrology - Category: Urology & Nephrology Source Type: research
The objective of the study was to test whether SLC9A3 variants cause Taiwanese CBAVD. Materials and Methods: Six-month-old Slc9a3 -/-male mice were used to evaluate the effect of long-term SLC9A3 loss on the reproductive system. A case-control cohort of 29 men with CBAVD and 32 fertile men were genotyped for SLC9A3 variants. Results: SLC9A3 was expressed and localized in the apical border of the epithelium of human vas deferens and glandular epithelium of the seminal vesicle. SLC9A3 deficiency specifically induces atrophy of vas deferens and unfolding of seminal vesicle mucosa in mice. Loss of SLC9A3 increased th...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
ConclusionThis study illustrates the significance of all exon sequencing inCFTR andADGRG2. A picture of the genetic spectrum of Chinese CAVD patients and the most common mutations can be described, which are different from Caucasian cohorts and Chinese CF patients.
Source: Andrology - Category: Urology & Nephrology Authors: Tags: Original Article Source Type: research
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