X/autosomal translocations in the Xq critical region associated with premature ovarian failure fall within and outside genes.

Premature ovarian failure curtails female reproductive life and is often linked to balanced Xq/autosomal translocations in a critical region. We mapped regions around translocations at the edges of this zone (one in Xq13.3, two in Xq26) in large-insert clones and analyzed their sequence. One Xq26 region is extensively transcribed and, in agreement with a recent independent analysis, the breakpoint interrupts a gene that encodes a widely expressed peptidase. In contrast 430 kb around the second Xq26 breakpoint has no putative or detected gene content. In 260 kb around the Xq13 translocation, the breakpoint falls among a cluster of repetitive elements at least 59 kb from the only detected gene (a rarely expressed T-box family transcription factor). We discuss our results in relation to models that ascribe premature ovarian failure to interruption of ovarian genes or to a failure of interactions involving DNA of the critical region during follicle development.