An exome-wide exploration of cases of primary ovarian insufficiency uncovers novel sequence variants and candidate genes.,Clinical Genetics

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An exome-wide exploration of cases of primary ovarian insufficiency uncovers novel sequence variants and candidate genes.
Clinical Genetics ( IF 2.9 ) Pub Date : 2020-07-02 , DOI: 10.1111/cge.13803
Maria Isabel Alvarez-Mora _{1,

2} , Anne-Laure Todeschini _{3,

4} , Sandrine Caburet _{3,

4} , Lilach Peled Perets ₅ , Montserrat Mila ₂ , Johnny S Younis _{6,

7} , Stavit Shalev _{4,

8} , Reiner A Veitia _{3,

4,

9}

Affiliation

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.

中文翻译：

对原发性卵巢功能不全病例进行的全基因组探索发现了新的序列变异和候选基因。

原发性卵巢功能不全（POI）意味着40岁之前的女性月经停止数月，这是不孕的主要原因。整个外显子组测序（WES）的使用促进了遗传因素对POI贡献的研究。在这里，为了发现新的致病性致病变异和风险等位基因，已对12例家族性POI患者（8例无关指标病例和两对姐妹）和6例早期绝经和有POI家族史的妇女（4例病例和1例）进行了WES。对姐妹）。鉴定了NR5A1和MCM9基因的可能致病变异以及INHA的变异需要进一步调查。此外，我们已经在15个家族病例中的3个中识别出一个以上的候选变体。综上所述，我们的结果突出了POI的遗传异质性和更年期早期，并且除了单基因遗传外，还支持此类条件的寡聚遗传的假说。

更新日期：2020-08-27

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