A susceptibility gene for premature ovarian failure (POF) maps to proximal Xq28.

Terminal deletions of the long arm of the human X chromosome have been described in women with premature ovarian failure (POF). We report here the molecular characterization of an inherited deletion in two affected women and in their mother. The two daughters presented secondary amenorrhea at 17 or 22 years respectively, while the mother was fertile. She had four children, but she eventually had premature menopause at 43 years of age. The fine molecular analysis of the deletion showed that the three women carried an identical deletion. We conclude that the phenotypic difference within the family must be attributed to genetic or environmental factors and not to the presence of different extent deletions. By comparison with other deletions in the region, we map a susceptibility gene for POF to 4.5 Mb, in the distal part of Xq.