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Sci Rep:在一个大的巴基斯坦家族中,与X染色体连锁的AGDRG2变异和梗阻性无精症研究

2018-11-14 AlexYang MedSci原创

最近,有研究人员在一个大的巴基斯坦家族中进行了全外显子组测序,并鉴定了一个引起镜子缺乏和男性不育的遗传病因。研究人员对3名不育的男性进行了精液分析、激素测试、睾丸组织学研究、超声诊断、染色体核型分析、Y染色体微缺失和CFTR测试。临床测试诊断为梗阻性无精子症(OA)。为了鉴定病因,研究人员对2名不育兄弟和2名课余家族成员进行了全外显子组测序(WES),并通过Sanger测序进行了分离分析和变异确定

最近,有研究人员在一个大的巴基斯坦家族中进行了全外显子组测序,并鉴定了一个引起镜子缺乏和男性不育的遗传病因。

研究人员对3名不育的男性进行了精液分析、激素测试、睾丸组织学研究、超声诊断、染色体核型分析、Y染色体微缺失和CFTR测试。临床测试诊断为梗阻性无精子症(OA)。为了鉴定病因,研究人员对2名不育兄弟和2名课余家族成员进行了全外显子组测序(WES),并通过Sanger测序进行了分离分析和变异确定。研究发现,WES数据分析表明了具有3个候选基因的变异。研究人员认为,一个与X染色体连锁的ADGRG2基因的无义变异 c.2440C>T(p.Arg814*)是最可能的遗传病因。据预测,该变异导致关键转膜区域的294个氨基酸缺失。另外,Adgrg2敲除小鼠由于阻塞性液体停滞引起精子缺失。对睾丸的组织学分析阐释了精子发生严重减少,这与人类和小鼠敲除表型一致。ADGRG2无义变异在最大的人类数据库中并没记录。在更多的家族成员中对新无义变异进行分析发现,该变异与所有患OA的男性共分离。该变异的致病本质由蛋白转膜结构域的缺失和独特的超声结果支撑。

最后,研究人员指出,他们的研究阐释了WES在发现无精子症遗传病因中的有效性。

原始出处:

Muhammad Jaseem Khan, Nijole Pollock, Huaiyang Jiang et al. X-linked ADGRG2 mutation and obstructive azoospermia in a large Pakistani family. Sci Rep. 2 Nov 2018.

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    2019-06-09 Tamikia
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    2018-11-16 清风拂面

    谢谢分享学习

    0

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    2018-11-16 tsing_hit
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