Laissue Paul, Christin-Maitre Sophie, Touraine Philippe, Kuttenn Frederique, Ritvos Olli, Aittomaki Kristiina, Bourcigaux Nathalie, Jacquesson Laetitia, Bouchard Philippe, Frydman Rene, Dewailly Didier, Reyss Anne-Céline, Jeffery Luke, Bachelot Anne, Massin Nathalie, Fellous Marc, Veitia Reiner A
INSERM 709, Genomics and Epigenetics of Placentary Pathology, Hôpital Cochin, Pavillon Baudelocque, 123 Bd de Port Royal, 75014, Paris, France.
Eur J Endocrinol. 2006 May;154(5):739-44. doi: 10.1530/eje.1.02135.
Mutations in bone morphogenic protein 15 (BMP15) and growth/differentiation factor 9 (GDF9) lead to altered fertility in animal models. In the human, a heterozygous point mutation of BMP15 has been associated with premature ovarian failure (POF).
We have directly sequenced both genes in a cohort of 203 POF patients presenting with primary or secondary amenorrhea and high FSH levels and in a control population including 54 women with regular menstrual cycles who had at least one child.
We have identified several heterozygous variants. One alteration in GDF9 (S186Y) and one in BMP15 (L148P) may have pathogenic effects as both positions are conserved in vertebrate species, ranging from the chicken to mammals. These variants were absent in the control samples. We also found synonymous and neutral substitutions.
We propose that although mutations in BMP15 and GDF9 are not a major cause of ovarian insufficiency, they may be involved in POF.
骨形态发生蛋白15（BMP15）和生长/分化因子9（GDF9）的突变会导致动物模型的生育能力改变。在人类中，BMP15的杂合点突变与卵巢早衰（POF）有关。
我们对203例表现为原发性或继发性闭经且促卵泡生成素（FSH）水平升高的POF患者以及54例月经周期规律且至少育有一个孩子的对照人群的两个基因进行了直接测序。
我们鉴定出了几种杂合变异。GDF9中的一种改变（S186Y）和BMP15中的一种改变（L148P）可能具有致病作用，因为从鸡到哺乳动物的脊椎动物物种中这两个位置都是保守的。这些变异在对照样本中不存在。我们还发现了同义替换和中性替换。
我们提出，虽然BMP15和GDF9的突变不是卵巢功能不全的主要原因，但它们可能与POF有关。
