USP26基因中的一种新型错义突变与非梗阻性无精子症相关。
A Novel Missense Mutation in USP26 Gene Is Associated With Nonobstructive Azoospermia.
作者信息
Ma Qian, Li Yuchi, Guo Huan, Li Cailing, Chen Jianbo, Luo Manling, Jiang Zhimao, Li Honggang, Gui Yaoting
机构信息
Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, PR China.
The Family Planning Research Institute/Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
出版信息
Reprod Sci. 2016 Oct;23(10):1434-41. doi: 10.1177/1933719116641758. Epub 2016 Apr 18.
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.
目的
本研究旨在评估泛素特异性蛋白酶26（USP26）基因变异是否与非梗阻性无精子症（NOA）相关。
方法
本研究纳入了776例被诊断为NOA的患者和709例经证实有生育能力的男性。通过选定的外显子测序鉴定包括USP26在内的不育相关基因的遗传变异。在Hela和TM4细胞中，通过免疫沉淀和荧光素酶测定检测USP26突变对雄激素受体（AR）结合、泛素化和转录活性的影响。
结果
在NOA患者中鉴定出6种新的错义突变和1种USP26独特的新同义突变。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
一种新的USP26变体p.R344W可能通过影响AR功能与NOA相关。
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