Fragile x-associated premature ovarian failure in a large Turkish cohort: Findings of Hacettepe Fragile X Registry

Objective: To determine frequency of fragile X associated premature ovarian insufficiency (FXPOI) among Turkish premutation carriers.

Study design: FMR1 premutation is the single most common genetic cause of POI (FXPOI). Fragile X Registry at Hacettepe University has been reviewed for the frequency of FXPOI among female premutation carriers. Since 1991 when FMR1 testing was available, 760 individuals from 243 families have been registered. Actual data on menstrual status of female premutation carriers were gathered and analysed.

Results: Among 314 premutation-bearing females in the cohort, 268 could be reached for an update of their menstrual history; 107 adults were 40 or younger and 156 were older than 40 years of age, whereas the remaining 5 patients were prepubertal. Among 263 postpubertal females with premutations, 90 women stopped menstruating before or at 40 years of age (premature ovarian failure - POF), constituting 34.2% of our cohort. Additionally, one carrier of a gray zone allele experienced FXPOI. History of twinning was present once in 18 women (5.7%) and twice in two women (0.6%), one of the latter interestingly bearing a full-mutation.

Conclusions: FXPOI rates in the present cohort are higher than those reported in other populations. Higher FXPOI rates in Turkish premutation carriers might be a reflection of younger mean menopause age and higher POI rates in otherwise healthy Turkish women. Since POI is much more frequent among premutation carriers than in general population, testing for CGG repeat expansions in FMR1 should be included in the work-up.