Novel Hemizygous Mutations of TEX11 Cause Meiotic Arrest and Non-obstructive Azoospermia in Chinese Han Population.
Novel Hemizygous Mutations of TEX11 Cause Meiotic Arrest and Non-obstructive Azoospermia in Chinese Han Population.
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TEX11的新半合子突变导致中国汉族人群减数分裂停滞和非梗阻性无精症
DOI：
10.3389/fgene.2021.741355
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发表时间：
2021
影响因子：
3.7
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Ji Z;Yao C;Yang C;Huang C;Zhao L;Han X;Zhu Z;Zhi E;Liu N;Zhou Z;Li Z
睾丸表达基因11（TEX11）突变与非梗阻性无精子症（NOA）和减数分裂阻滞有关。小鼠中TEX11的类似突变损害减数分裂，并且可以通过体外扩增SSC和基因治疗来挽救。然而，由于缺乏对大量亚洲患者的基因筛查（包括家系分析）和适当的功能评估，限制了TEX11突变筛查的临床应用。因此，我们在479例NOA患者中进行了全外显子组测序（WES），并在来自三个家庭的三对兄弟姐妹中确定了TEX11的三个新突变（两个剪接突变和一个错义突变），并在四个散发性NOA影响病例中确定了TEX11的四个新致病突变（三个移码突变和一个无义突变）。家庭成员中的新变体按疾病表型进行分离，预计所有七种突变都是致病性的。组织学分析显示，3例TEX11突变患者发生了减数分裂阻滞。通过Western blot验证了导致蛋白质截短和减数分裂特异性孢子形成结构域SPO22缺陷的四个突变。总共，我们发现479例NOA患者中有7例（1.5%）携带TEX11突变。我们的研究扩展了亚洲NOA患者TEX11基因突变的知识。TEX11的高患病率和X连锁遗传模式表明，TEX11可能被纳入NOA患者的遗传筛查组，用于临床评估。
Testis-expressed gene 11 (TEX11) mutation has been associated with non-obstructive azoospermia (NOA) and meiotic arrest. An analogous mutation of TEX11 in the mouse impairs meiosis and can be rescued by in vitro expansion of SSCs and gene therapy. However, a lack of genetic screening of a large cohort of Asian patients (including pedigree analysis) and proper functional evaluation limit the clinical application of TEX11 mutation screening. Thus, we performed whole-exome sequencing (WES) in 479 patients with NOA and identified three novel mutations (two splicing mutations and one missense mutation) in TEX11 in three pairs of siblings from three families and four novel pathogenic mutations (three frameshift mutations and a non-sense mutation) of TEX11 in four sporadic NOA-affected cases. Novel variants among family members were segregated by disease phenotype, and all the seven mutations were predicted to be pathogenic. Histological analysis showed that three patients with TEX11 mutations underwent meiotic arrest. The four mutations that resulted in protein truncations and defective meiosis-specific sporulation domain SPO22 were validated by Western blot. In total, we find seven of 479 patients of NOA (1.5%) carrying TEX11 mutations. Our study expands the knowledge of mutations of TEX11 gene in Asian patients with NOA. The high prevalence and X-linked inherited mode indicated that TEX11 might be included in genetic screening panels for the clinical evaluation of patients with NOA.
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影响因子：
14.9
作者：
Mistry J;Chuguransky S;Williams L;Qureshi M;Salazar GA;Sonnhammer ELL;Tosatto SCE;Paladin L;Raj S;Richardson LJ;Finn RD;Bateman A
通讯作者：
Bateman A
DOI：
10.1056/nejmoa1406192
发表时间：
2015-05-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Yatsenko AN;Georgiadis AP;Röpke A;Berman AJ;Jaffe T;Olszewska M;Westernströer B;Sanfilippo J;Kurpisz M;Rajkovic A;Yatsenko SA;Kliesch S;Schlatt S;Tüttelmann F
通讯作者：
Tüttelmann F
影响因子：
6.7
作者：
Stephen, Elizabeth Hervey;Chandra, Anjani
通讯作者：
Chandra, Anjani
影响因子：
10.5
作者：
Yang, Fang;Gell, Katarina;Wang, Peijing Jeremy
通讯作者：
Wang, Peijing Jeremy
DOI：
10.1007/s11825-018-0181-7
发表时间：
2018
期刊：
Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V
影响因子：
--
作者：
Tüttelmann F;Ruckert C;Röpke A
通讯作者：
Röpke A