title: A novel FOXL2 gene mutation and BMP15 variants in a woman with primary ovarian insufficiency and blepharophimosis-ptosis-epicanthus inversus syndrome.
abstract: OBJECTIVE
  This study aims to search for mutations in relevant genes in a woman with primary ovarian insufficiency (POI) and blepharophimosis-ptosis-epicanthus inversus syndrome (BPES).
  
  
  METHODS
  This study reports on the case of a woman with POI, BPES, and autoimmune endocrine disorder. Bidirectional sequencing of the coding regions and intron/exon boundaries of FOXL2 and BMP15 genes and hormonal assays for the measurement of follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone, Δ4-androstenedione, and dehydroepiandrosterone sulfate were employed.
  
  
  RESULTS
  A novel de novo heterozygous deletion (p.K150Rfs*121) in the FOXL2 gene was identified to coexist with two BMP15 gene variants located in the same allele (c.-9C>G; p.N103S).
  
  
  CONCLUSIONS
  The novel, de novo FOXL2 gene mutation (p.K150Rfs*121) expands the spectrum of molecular defects identified in women with BPES. Coexisting gene variants in POI-related genes, such as BMP15, may act synergistically and explain the observed phenotypic variability in women with BPES (ie, BPES with or without POI). The concept of digenic inheritance suggested herein has been previously introduced for other nosologies such as hypogonadotrophic hypogonadism. Endocrine autoimmunity might also contribute to the POI phenotype.
authors.affiliation: 1First Department of Pediatrics, School of Medicine, University of Athens, "Aghia Sophia" Children's Hospital, Athens, Greece 2Department of Medical Genetics, School of Medicine, University of Athens, "Aghia Sophia" Children's Hospital, Athens, Greece 3Private Practice, Athens, Greece 4Research Institute for the Study of Genetic and Malignant Diseases of Childhood, "Aghia Sophia" Children's Hospital, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Settas
authors.forename: Margarita
authors.initials: M
authors.lastname: Anapliotou
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Kanavakis
authors.forename: Helen
authors.initials: H
authors.lastname: Fryssira
authors.forename: Christalena
authors.initials: C
authors.lastname: Sofocleous
authors.forename: Catherine
authors.initials: C
authors.lastname: Dacou-Voutetakis
authors.forename: George P
authors.initials: GP
authors.lastname: Chrousos
authors.forename: Antonis
authors.initials: A
authors.lastname: Voutetakis
mesh_terms: D016569:Blepharophimosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005143:Eyelids / Q000002:abnormalities*; D005192:Family Health; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D017354:Point Mutation; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D012868:Skin Abnormalities / Q000235:genetics*; D013577:Syndrome
chemical_list: C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors