title: A potential functional association between mutant BMPR2 and primary ovarian insufficiency.
abstract: 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.
  
  
  BACKGROUND
  POI: primary ovarian insufficiency; ER: endoplasmic reticulum; NGS: next generation sequencing.
authors.affiliation: a Centro de Investigación en Genética y Genómica-CIGGUR, Grupo GENIUROS, Escuela de Medicina y Ciencias de la Salud , Universidad del Rosario , Bogotá , Colombia.
authors.forename: Liliana Catherine
authors.initials: LC
authors.lastname: Patiño
authors.affiliation: a Centro de Investigación en Genética y Genómica-CIGGUR, Grupo GENIUROS, Escuela de Medicina y Ciencias de la Salud , Universidad del Rosario , Bogotá , Colombia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Silgado
authors.affiliation: a Centro de Investigación en Genética y Genómica-CIGGUR, Grupo GENIUROS, Escuela de Medicina y Ciencias de la Salud , Universidad del Rosario , Bogotá , Colombia.
authors.forename: Paul
authors.initials: P
authors.lastname: Laissue
mesh_terms: D000818:Animals; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics* / Q000378:metabolism; D016466:CHO Cells; D003412:Cricetulus; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D009154:Mutation; D016649:Primary Ovarian Insufficiency / Q000235:genetics*
chemical_list: D052006:Bone Morphogenetic Protein Receptors, Type II
keywords: BMPR2; primary ovarian insufficiency (POI); protein-like aggregation