Mutant cohesin in premature ovarian failure.
Mutant cohesin in premature ovarian failure.
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DOI：
10.1056/nejmoa1309635
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发表时间：
2014-03-06
期刊：
影响因子：
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通讯作者：
Vilain E
中科院分区：
文献类型：
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作者：
Caburet S;Arboleda VA;Llano E;Overbeek PA;Barbero JL;Oka K;Harrison W;Vaiman D;Ben-Neriah Z;García-Tuñón I;Fellous M;Pendás AM;Veitia RA;Vilain E
卵巢早衰是女性不孕的主要原因。对于大多数患者来说，这种疾病的遗传原因仍然未知。通过对患有遗传性卵巢早衰的大型近亲家族进行全外显子组序列分析，我们发现了一个纯合的 1-bp 缺失，可诱导 7 号染色体上的 STAG3 发生移码突变。STAG3 编码粘连蛋白环的减数分裂特异性亚基，可确保正确的姐妹染色单体凝聚力。缺乏Stag3的雌性小鼠是不育的，它们的胎儿卵母细胞在早期I早期被停滞，导致1周龄时卵母细胞耗尽。
Premature ovarian failure is a major cause of female infertility. The genetic causes of this disorder remain unknown in most patients. Using whole-exome sequence analysis of a large consanguineous family with inherited premature ovarian failure, we identified a homozygous 1-bp deletion inducing a frameshift mutation in STAG3 on chromosome 7. STAG3 encodes a meiosis-specific subunit of the cohesin ring, which ensures correct sister chromatid cohesion. Female mice devoid of Stag3 are sterile, and their fetal oocytes are arrested at early prophase I, leading to oocyte depletion at 1 week of age.