Alvarez-Mora Maria Isabel, Todeschini Anne-Laure, Caburet Sandrine, Perets Lilach Peled, Mila Montserrat, Younis Johnny S, Shalev Stavit, Veitia Reiner A
Genetics Service, Hospital 12 de Octubre, Madrid, Spain.
Department of Biochemistry and Molecular Genetics, Hospital Clinic of Barcelona and IDIBAPS, Spain.
Clin Genet. 2020 Sep;98(3):293-298. doi: 10.1111/cge.13803. Epub 2020 Jul 28.
Primary ovarian insufficiency (POI) implies the cessation of menstruation for several months in women before the age of 40 years and is a major cause of infertility. The study of the contribution of genetic factors to POI has been fueled by the use of whole exome sequencing (WES). Here, to uncover novel causative pathogenic variants and risk alleles, WES has been performed in 12 patients with familial POI (eight unrelated index cases and two pairs of sisters) and six women with early menopause and family history of POI (four index cases and one pair of sisters). Likely causative variants in NR5A1 and MCM9 genes were identified as well as a variant in INHA that requires further investigation. Moreover, we have identified more than one candidate variant in 3 out of 15 familial cases. Taken together, our results highlight the genetic heterogeneity of POI and early menopause and support the hypothesis of an oligogenic inheritance of such conditions, in addition to monogenic inheritance.
原发性卵巢功能不全（POI）指40岁之前女性月经停止数月，是不孕的主要原因。全外显子组测序（WES）的应用推动了对POI遗传因素贡献的研究。在此，为了发现新的致病致病变异和风险等位基因，对12例家族性POI患者（8例无亲缘关系的索引病例和2对姐妹）以及6例有POI家族史的早绝经女性（4例索引病例和1对姐妹）进行了WES检测。鉴定出NR5A1和MCM9基因中可能的致病变异以及INHA中的一个需要进一步研究的变异。此外，在15例家族性病例中的3例中鉴定出不止一个候选变异。综上所述，我们的结果突出了POI和早绝经的遗传异质性，并支持除单基因遗传外这些情况的寡基因遗传假说。
