Department of Genomic Medicine and Familial Cancer Centre, Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.
Department of Molecular Pathology, Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.
J Assist Reprod Genet. 2021 Jun;38(6):1539-1543. doi: 10.1007/s10815-021-02144-x. Epub 2021 Apr 1.
Premature or primary ovarian insufficiency (POI) affects approximately 1% of women and can be due to a variety of causes. Genetic causes include syndromic and non-syndromic POI. There are several promising candidate genes for whom a clear Mendelian association with non-syndromic POI has not yet been conclusively established, including GDF9. GDF9 is an oocyte-secreted factor and is part of the TGF-beta superfamily of morphogens. It has an important role in follicular development and granulosa cell maturation. We report the case of two siblings with primary ovarian insufficiency (POI) and a homozygous truncating variant in GDF9 (c.604C>T; p.(Gln202*). This report helps establish a clear gene-disease association between GDF9 and POI and argues for routine evaluation for GDF9 variants in patients undergoing genomic investigation for POI.
原发性或早发性卵巢功能不全（POI）影响约 1%的女性，其病因多种多样。遗传病因包括综合征型和非综合征型 POI。有几个有希望的候选基因，尽管它们与非综合征型 POI 有明确的孟德尔相关性，但尚未得到明确证实，其中包括 GDF9。GDF9 是一种卵母细胞分泌的因子，是转化生长因子-β（TGF-β）形态发生素超家族的一部分。它在卵泡发育和颗粒细胞成熟中起重要作用。我们报告了两例原发性卵巢功能不全（POI）的同胞患者，他们携带 GDF9 中的纯合截断变异（c.604C>T；p.(Gln202*）。本报告有助于在 GDF9 和 POI 之间建立明确的基因-疾病相关性，并主张对接受 POI 基因组研究的患者进行 GDF9 变异的常规评估。
