A Novel Missense Mutation in USP26 Gene Is Associated With Nonobstructive Azoospermia
A Novel Missense Mutation in USP26 Gene Is Associated With Nonobstructive Azoospermia
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USP26 基因中的一种新的错义突变与非梗阻性无精子症相关
DOI：
10.1177/1933719116641758
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发表时间：
2016-10-01
影响因子：
2.9
通讯作者：
Gui, Yaoting
中科院分区：
文献类型：
--
作者：
Ma, Qian;Li, Yuchi;Gui, Yaoting
目的：本研究的目的是评估泛素特异性肽酶26（USP 26）基因变异是否与非梗阻性无精子症（NOA）相关。方法：776例诊断为NOA的患者和709例已证实生育的男性被纳入本研究。通过选择性外显子测序鉴定不育相关基因（包括USP 26）的遗传变异。采用免疫沉淀和荧光素酶法检测USP26突变对Hela和TM4细胞雄激素受体（AR）结合、泛素化和转录活性的影响。结果：在NOA患者中发现了6个USP26基因的新错义突变和1个新的同义突变。在这些错义突变中，USP26 R344W显著降低了USP26与AR的结合亲和力和去泛素化活性，从而消除了USP26对Hela和TM4细胞中AR转录活性的抑制作用。结论：USP26新变异体p.R344W可能通过影响AR功能与NOA相关。
Objective: The aim of this study was to evaluate whether ubiquitin-specific peptidase 26 (USP26) gene variations were associated with nonobstructive azoospermia (NOA). Methods: Seven hundred and seventy-six patients diagnosed with NOA and 709 proven fertile men were included in this study. Genetic variations of infertility-related genes, including USP26, were identified by selected exonic sequencing. The effects of USP26 mutations on androgen receptor (AR) binding, ubiquitination, and transcriptional activity were detected by immunoprecipitation and luciferase assay in Hela and TM4 cells. Results: Six novel missense mutations and 1 novel synonymous mutation of USP26 unique to the patients with NOA were identified. Of these missense mutations, USP26 R344W remarkably reduced the binding affinity and deubiquitinating activity of USP26 to AR, thus eliminated the inhibitory effect of USP26 on transcriptional activity of AR in Hela and TM4 cells. Conclusion: A novel USP26 variant p.R344W is associated with NOA probably through affecting AR function.