The Association of FMR1 Gene Low-Normal and High-Normal Alleles with Ovarian Dysfunctions: A Retrospective Analysis...

The FMR1 gene, located at Xq27.3, exhibits varying phenotypic effects based on CGG repeat expansions. The aim of this study was to determine the triple repeat distribution in females and to evaluate the relationship between low-normal (n < 26) and/or high-normal (n > 34) alleles and various ovarian dysfunctions.

A retrospective analysis was conducted on 152 females tested for FMR1 CGG repeats at Konya City Hospital (2021-2022). Normal/intermediate alleles were categorized as low-normal, normal, or high-normal and their distributions were analyzed in women presenting with various forms of ovarian dysfunction, with a particular focus on premature ovarian insufficiency (POI).

Two (1.4%) cases had full mutations, and nine (6.5%) carried premutations, with POI present in 55.6% of premutation carriers. POI was the most common referral reason (54.7%). The median value for short and long alleles was observed to be 29-31. The low-normal allele frequency was 13.6% (POI), 18.8% (primary amenorrhea), 25% (secondary amenorrhea), and 14.3% (infertility), while high-normal alleles were 12.1% (POI), 12.5% (primary amenorrhea), 5% (secondary amenorrhea), and 0% (infertility).

This study reinforces the role of FMR1 premutations in POI etiology and suggests a potential association between low-normal/high-normal CGG repeats and various ovarian dysfunctions. It also represents the first analysis of normal/intermediate range repeat distribution in a Turkish cohort.