Dataset Information

Targeted next-generation sequencing panel screening of 668 Chinese patients with non-obstructive azoospermia.

ABSTRACT:

Purpose

We aimed (1) to determine the molecular diagnosis rate and the recurrent causative genes of patients with non-obstructive azoospermia (NOA) using targeted next-generation sequencing (NGS) panel screening and (2) to discuss whether these genes help in the prognosis for microsurgical testicular sperm extraction (micro-TESE).

Methods

We used NGS panels to screen 668 Chinese men with NOA. Micro-TESE outcomes for six patients with pathogenic mutations were followed up. Functional assays were performed for two NR5A1 variants identified: p.I224V and p.R281C.

Results

Targeted NGS panel sequencing could explain 4/189 (2.1% by panel 1) or 10/479 (2.1% by panel 2) of the patients with NOA after exclusion of karyotype abnormalities and Y chromosome microdeletions. Almost all mutations detected were newly described except for NR5A1 p.R281C and TEX11 p.M156V. Two missense NR5A1 mutations-p.R281C and p.I244V-were proved to be deleterious by in vitro functional assays. Mutations in TEX11, TEX14, and NR5A1 genes are recurrent causes of NOA, but each gene explains only a very small percentage (less than 4/668; 0.6%). Only the patient with NR5A1 mutations produced viable spermatozoa through micro-TESE, but other patients with TEX11 and TEX14 had poor micro-TESE prognoses.

Conclusions

A targeted NGS panel is a feasible diagnostic method for patients with NOA. Because each gene implicated explains only a small proportion of such cases, more genes should be included to further increase the diagnostic rate. Considering previous reports, we suggest that only a few genes that are directly linked to meiosis can indicate poor micro-TESE prognosis, such as TEX11, TEX14, and SYCE1.

SUBMITTER: An M

PROVIDER: S-EPMC8417191 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

Targeted next-generation sequencing panel screening of 668 Chinese patients with non-obstructive azoospermia.

An Miao M Liu Yidong Y Zhang Ming M Hu Kai K Jin Yan Y Xu Shiran S Wang Hongxiang H Lu Mujun M

Journal of assisted reproduction and genetics 20210316 8

<h4>Purpose</h4>We aimed (1) to determine the molecular diagnosis rate and the recurrent causative genes of patients with non-obstructive azoospermia (NOA) using targeted next-generation sequencing (NGS) panel screening and (2) to discuss whether these genes help in the prognosis for microsurgical testicular sperm extraction (micro-TESE).<h4>Methods</h4>We used NGS panels to screen 668 Chinese men with NOA. Micro-TESE outcomes for six patients with pathogenic mutations were followed up. Function ...[more]

PMID: 33728612

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Project description:BackgroundAt present, the hereditary hearing loss homepage, ( https://hereditaryhearingloss.org/ ), includes 258 deafness genes and more than 500 genes that have been reported to cause deafness. With few exceptions, the region-specific distributions are unclear for many of the identified variants and genes.MethodsHere, we used a custom capture panel to perform targeted sequencing of 518 genes in a cohort of 879 deaf Chinese probands who lived in Yunnan. Mutation sites of the parents were performed by high-throughput sequencing and validated by Sanger sequencing.ResultsThe ratio of male to female patients was close to 1:1 (441:438) and the age of onset was mainly under six. Most patients (93.5%) were diagnosed with moderate to severe deafness. Four hundred and twenty-eight patients had variants in a deafness gene, with a detection rate of 48.7%. Pathogenic variants were detected in 98 genes and a number of these were recurrent within the cohort. However, many of the variants were rarely observed in the cohort. In accordance with the American College of Medical Genetics and Genomics, pathogenic, likely pathogenic and variants of uncertain significance accounted for 34.3%, 19.3% and 46.4% of all detected variants, respectively. The most common genes included GJB2, SLC26A4, MYO15A, MYO7A, TMC1, CDH23, USH2A and WFS1, which contained variants in more than ten cases. The two genes with the highest mutation frequency were GJB2 and SLC26A4, which accounted for 28.5% (122/428) of positive patients. We showed that more than 60.3% of coding variants were rare and novel. Of the variants that we detected, 80.0% were in coding regions, 17.9% were in introns and 2.1% were copy number variants.ConclusionThe common mutation genes and loci detected in this study were different from those detected in other regions or ethnic groups, which suggested that genetic screening or testing programs for deafness should be formulated in accordance with the genetic characteristics of the region.

Dataset Information

Targeted next-generation sequencing panel screening of 668 Chinese patients with non-obstructive azoospermia.

Purpose

Methods

Results

Conclusions

Publications

Targeted next-generation sequencing panel screening of 668 Chinese patients with non-obstructive azoospermia.

Similar Datasets

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