Patiño Liliana Catherine, Silgado Daniel, Laissue Paul
a Centro de Investigación en Genética y Genómica-CIGGUR, Grupo GENIUROS, Escuela de Medicina y Ciencias de la Salud , Universidad del Rosario , Bogotá , Colombia.
Syst Biol Reprod Med. 2017 Jun;63(3):145-149. doi: 10.1080/19396368.2017.1291767. Epub 2017 Mar 17.
Primary ovarian insufficiency (POI) affects ~1% of women in the general population. Despite numerous attempts at identifying POI genetic aetiology, coding mutations in only a few genes have been functionally related to POI pathogenesis. It has been suggested that mutant BMPR2 might contribute towards the phenotype. Several BMP15 (a BMPR2 ligand) coding mutations in human species have been related to POI pathogenesis. The BMPR2 p.Ser987Phe mutation, previously identified in a woman with POI, might therefore lead to cellular dysfunction contributing to the phenotype. To explore such an assumption, the present study assessed potential pathogenic subcellular localization/aggregation patterns associated with the p.Ser987Phe mutant form of BMPR2 in a relevant model for studying ovarian function. A significant increase in protein-like aggregation patterns was identified at the endoplasmic reticulum (ER) which permitted us to establish, for the first time, a potential functional association between mutant BMPR2 and POI aetiology. Since BMPR2 mutant forms were previously related to idiopathic pulmonary arterial hypertension, BMPR2 mutations may be related to an as-yet-to-be described syndromic form of POI involving pulmonary dysfunction. Additional assays are necessary to confirm that BMPR2 abnormal subcellular patterns are composed by aggregates.
POI: primary ovarian insufficiency; ER: endoplasmic reticulum; NGS: next generation sequencing.
原发性卵巢功能不全（POI）影响普通人群中约1%的女性。尽管人们多次尝试确定POI的遗传病因，但只有少数基因的编码突变在功能上与POI的发病机制相关。有人提出，突变的BMPR2可能导致该表型。人类中的几种BMP15（一种BMPR2配体）编码突变与POI的发病机制有关。因此，先前在一名POI女性中鉴定出的BMPR2 p.Ser987Phe突变可能导致细胞功能障碍，从而导致该表型。为了探究这一假设，本研究在一个研究卵巢功能的相关模型中评估了与BMPR2的p.Ser987Phe突变形式相关的潜在致病性亚细胞定位/聚集模式。在内质网（ER）中发现蛋白质样聚集模式显著增加，这使我们首次确定了突变的BMPR2与POI病因之间的潜在功能关联。由于BMPR2突变形式先前与特发性肺动脉高压有关，BMPR2突变可能与一种尚未描述的涉及肺功能障碍的POI综合征形式有关。需要进一步的试验来确认BMPR2异常亚细胞模式是由聚集体组成的。
POI：原发性卵巢功能不全；ER：内质网；NGS：下一代测序。
