Mutation analysis of two candidate genes for premature ovarian failure, DACH2 and POF1B

BACKGROUND: Balanced X;autosome translocations interrupting the 'critical
region' of the long arm of the human X chromosome are often associated with
premature ovarian failure (POF). However, the mechanisms leading to X-linked
ovarian dysfunction are largely unknown, as the majority of the X chromosome
breakpoints have been mapped to gene-free genomic regions. A few genes have been
found to be interrupted, but their role has never been clarified. METHODS AND
RESULTS: By fine mapping of the X chromosome breakpoint of an X;autosome
balanced translocation, we identified a new interrupted gene, POF1B. We
performed a mutation analysis of POF1B and of another gene previously
identified, DACH2, localized approximately 700 kb distal in Xq21, in a cohort of
>200 Italian POF patients. Rare mutations were found in patients in both genes.
CONCLUSIONS: Our findings could not demonstrate any involvement of POF1B, but
suggest that rare mutations in the DACH2 gene may have a role in the POF
phenotype