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.