POF2 gene may be responsible for the ovarian phenotype of Turner syndrome.

A new gene, POF2, was identified by bioinformatic tools in the critical region for POF (Premature Ovarian Failure, OMIM 311360) in Xq21. The POF2 gene encodes a 589 aa putative protein with a large coiled-coil domain and no other homologies with known proteins. The new gene was found interrupted in the third intron by the breakpoint of a balanced X/1 translocation of a POF affected woman. Interestingly, RT-PCR experiments revealed the presence of a normal transcript in the patient which was not expected as the normal X chromosome is inactivated in balanced translocations. Investigation of the inactivation pattern of this new gene by RT-PCR amplification on different hybrid cell lines containing only the active or the inactive X chromosomes indicates that the POF2 gene is not subjected to X-inactivation. This evidence makes the POF2 gene a good candidate not only for the POF disease but also for the ovarian dysgenesis peculiar of the Turner Syndrome (TS). TS is associated with X chromosome monosomies and is a general belief that haploinsufficiency of specific genes normally required in double dosage is the cause of the pathology. Moreover the mutation analysis of the POF2 gene in a collection of 170 POF females with normal cariotype, revealed the presence of two missense mutations in three different patients with early onset of the disease. Taken together these results indicate that POF2 gene is a strong candidate for the normal development and/or function of the ovary.