早期卵巢缺陷中的NOBOX基因变异:依赖种族的见解
Pénélope Jordan1, Camille Verebi1, Sandrine Perol2
1Service de Médecine Génomique Des Maladies de Système Et d'Organe, Hôpital Cochin, APHP, Centre Université de Paris Cité, 123 Boulevard de Port-Royal, 75014, Paris, France.
Journal of assisted reproduction and genetics
|November 3, 2023
概括
NOBOX基因中的遗传变异与早产卵巢缺陷 (POI) 有关. 这项研究澄清了NOBOX变种的致病性,确定了具有POI发展不同风险的特定突变.
科学领域:
- 生殖遗传学 生殖遗传学
- 内分泌系疾病的基因组学
背景情况:
- 过早的卵巢衰竭 (POI) 影响40岁以下的女性的~1%.
- 遗传因素对POI有很大影响.
- NOBOX基因是POI的关键候选基因,但变异性致病性和透性尚未确定.
研究的目的:
- 在POI患者中研究NOBOX基因变异的致病性和透性.
- 将POI患者的NOBOX变异频率与一般人口的频率进行比较,考虑种族.
主要方法:
- 在810名POI患者的NOBOX基因整个编码区域的下一代测序.
- 变种频率与一般人口数据的比较,按种族分层.
主要成果:
- 确定了35种NOBOX变种,包括5种功能丧失变种.
- 171名POI患者 (25%) 携带至少一个NOBOX变种.
- 在POI患者中,某些误解变异的显著过度代表性,在p.(Arg44Leu),p.(Arg117Trp) 和p.(Asp452Asn) 中指出了种族变异.
结论:
- p. ((Arg44Leu) 可能是一种良性变体.
- 建议p. ((Asp452Asn) 和p. ((Arg117Trp) 是具有中等风险的致病变体,透率/表达力较低.
- p. ((Gly91Trp) 和 p. ((Gly152Arg) 被认为是具有中度功能影响的致病变体.
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