The Significance of Fragile X Mental Retardation Gene 1 CGG Repeat Sizes in the Normal and Intermediate Range in Women With Primary Ovarian Insufficiency

Primary ovarian insufficiency (POI) refers to the cessation of menses before the age of 40 years and occurs in 1 to 2 of women. The specific cause of POI is unknown in the majority of cases. Known causes include gene mutations of fragile X mental retardation 1 (FMR1), a gene located on the X chromosome. This gene codes for a protein essential for normal cognitive development and female reproductive function. FMR1contains a CCG trinucleotide segment in an untranslated region of its DNA that is repeated less than 45 times in normal individuals (normal range of repeats). Mutation of FMR1results in abnormal expansion of an unstable CGG triplet, leading to impaired cognitive and reproductive function. Between 55 and 200 CCG repeats is called premutation; affected individuals with premutation are at risk for POI and further expansion of repeats in subsequent generations. People with 45 to 54 CCG repeats (intermediate range of repeats) are considered to be at borderline risk for POI and further expansion of repeats.