Microdeletions in FMR2 may be a significant cause of premature ovarian failure

Genetic causes of premature ovarian failure (POF) include X chromosome dele tions and fragile X (FRAXA) premutations. While screening a cohort of women with POF for FRAXA premutations, a more distal trinucleotide repeat, FRAXE , was also tested. We found an unexpected excess of FRAXE alleles with appa rently fewer than 11 repeats in the POF group. However, sequence analysis o f these alleles showed that the excess was caused by three females who carr y cryptic deletions in FMR2, the gene associated with FRAXE. We propose tha t microdeletions within FMR2 may be a significant cause of premature ovaria n failure, being found in 1.5% of women with the condition, and in only 0.0 4% of the general female population. The deletions may affect transcription of either FMR2 or an adjacent gene.