Molecular cytogenetic definition of a translocation t(X;15) associated with premature ovarian failure

Objective To characterize the breakpoints of a t(X;15) found in a woman with premature ovarian failure (POF). Design Case report. Setting Molecular and cytogenetics unit in a university-affiliated hospital. Patient(s) A 19-year-old infertile woman presenting with a normal female phenotype but primary amenorrhea. Intervention(s) Molecular cytogenetic analyses and genetic counseling. Main Outcome Measure(s) Translocation t(X;15) defined by fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (array CGH). Result(s) Chromosome and FISH analysis revealed 46,XX, t(X;15)(Xq22.1;p11); the active X was translocated and had been inherited from her mother. Detailed molecular characterization by FISH showed that the NXF5 (nuclear RNA export factor 5) gene was contained in the clone spanning the breakpoint on the X chromosome. Conclusion(s) The NXF5 gene is an appealing candidate for POF because it shows functional homology with the FMR1 (fragile X mental retardation 1) gene. Further analyses of its expression as well as mutation screening in other POF patients will help to elucidate its role.