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

Abstract

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.

Molecular cytogenetic characterization of two Turner syndrome patients with mosaic ring X chromosome

“…4). Besides these critical region, breakpoints in Xq13-Xq27 due to balanced X, autosome translocation has been reported in cases of POF [32,33,35].…”

Loss of heterozygosity and microsatellite instability at the Xq28 and the A/G heterozygosity of the QM gene are associated with ovarian cancer

“…There has not been any LOH or MSI data for any of these four markers in the literature, although Xq28 has been reported to be associated with cancers in reproductive organs including the prostate, ovary and breast. [22][23][24][25] The fact that all 29 cases of ovarian cancer studied show at least one genetic alteration, either LOH or MSI, in at least one of the four microsatellite markers indicates that Xq28 may be highly relevant to ovarian cancer and that QM locus falls in a high LOH and MSI region. We have recently shown that the decrease in QM protein level, determined by immunohistochemistry, is associated with tumor grade of prostate cancer.…”

Falência ovariana precoce associada a deleção no braço longo do cromossomo: relato de dois casos e revisão da literatura

“…As deleções parciais do cromossomo X têm sido relatadas, sendo a maioria de casos isolados com herança familiar 3,4,6,8,13 . Nos casos descritos a ausência de história familiar de menopausa precoce parece indicar que se tratem de deleções de novo do cromossomo X, embora não tenha sido realizada a investigação genética dos pais das pacientes.…”

“…Isto foi sugerido em relato de deleção na região Xq28 no qual três mulheres de uma mesma família (mãe e duas fi lhas) apresentavam diferentes genótipos, apesar de serem afetadas por alteração genética idêntica. Neste relato a mãe teve menopausa prematura aos 43 anos, ao passo que as fi lhas entraram em amenorréia secundária aos 17 e 22 anos de idade 13 . Outro estudo também achou comportamento semelhante em mãe com menopausa precoce e fi lha com FOP, ambas com deleções em Xq26.2-q28 7 .…”