Study of the Genetic Etiology of Primary Ovarian Insufficiency: FMR1 Gene

Menopause is a period of women’s life characterized by the cessation of menses in a definitive way. The mean age for menopause is approximately 51 years. Primary ovarian insufficiency (POI) refers to ovarian dysfunction defined as irregular menses and elevated gonadotrophin levels before or at the age of 40 years. The etiology of POI is unknown but several genes have been reported as being of significance. The fragile X mental retardation 1 gene (FMR1) is one of the most important genes associated with POI. The FMR1 gene contains a highly polymorphic CGG repeat in the 5′ untranslated region of exon 1. Four allelic forms have been defined with respect to CGG repeat length and instability during transmission. Normal (5–44 CGG) alleles are usually transmitted from parent to offspring in a stable manner. The full mutation form consists of over 200 repeats, which induces hypermethylation of the FMR1 gene promoter and the subsequent silencing of the gene, associated with Fragile X Syndrome (FXS). Finally, FMR1 intermediate (45–54 CGG) and premutation (55–200 CGG) alleles have been principally associated with two phenotypes, fragile X tremor ataxia syndrome (FXTAS) and fragile X primary ovarian insufficiency (FXPOI).