The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome

In type I blepharophimosis/ptosis/epicanthus inversus syndrome (BPES), eyel id abnormalities are associated with ovarian failure. Type II BPES shows on ly the eyelid defects, but both types map to chromosome 3q23. We have posit ionally cloned a novel. putative winged helix/forkhead transcription factor gene, FOXL2, that is mutated to produce truncated proteins in type I famil ies and larger proteins in type II. Consistent with an involvement in those tissues, FOXL2 is selectively expressed in the mesenchyme of developing mo use eyelids and in adult ovarian follicles; in adult humans, it appears pre dominantly in the ovary. FOXL2 represents a candidate gene for the polled/i ntersex syndrome XX sex-reversal goat.