Investigation of <it>KIT</it> gene mutations in women with 46,XX spontaneous premature ovarian failure

• Main Authors: Nelson Lawrence M (Author), Vanevski Konstantina (Author), Vanderhoof Vien H (Author), Tong Zhi-Bin (Author), Shibanuma Kyoko (Author)
• Formato: Livro
• Publicado em: BMC, 2002-08-01T00:00:00Z.
• Assuntos: article
• Acesso em linha: Connect to this object online.
• Notes: 10.1186/1472-6874-2-8; 1472-6874
• Keywords: Gynecology and obstetrics; RG1-991; Public aspects of medicine; RA1-1270
• Source: BMC Women's Health, Vol 2, Iss 1, p 8 (2002)

<p>Abstract</p> <p>Background</p> <p>Spontaneous premature ovarian failure presents most commonly with secondary amenorrhea. Young women with the disorder are infertile and experience the symptoms and sequelae of estrogen deficiency. The mechanisms that give rise to spontaneous premature ovarian failure are largely unknown, but many reports suggest a genetic mechanism in some cases. The small family size associated with infertility makes genetic linkage analysis studies extremely difficult. Another approach that has proven successful has been to examine candidate genes based on known genetic phenotypes in other species. Studies in mice have demonstrated that c-kit, a transmembrane tyrosine kinase receptor, plays a critical role in gametogenesis. Here we test the hypothesis that human <it>KIT</it> mutations might be a cause of spontaneous premature ovarian failure.</p> <p>Methods and Results</p> <p>We examined 42 women with spontaneous premature ovarian failure and found partial X monosomy in two of them. In the remaining 40 women with known 46,XX spontaneous premature ovarian failure we evaluated the entire coding region of the <it>KIT</it> gene. We did this using polymerase chain reaction based single-stranded conformational polymorphism analysis and DNA sequencing. We did not identify a single mutation that would alter the amino acid sequence of the c-KIT protein in any of 40 patients (upper 95% confidence limit is 7.2%). We found one silent mutation at codon 798 and two intronic polymorphisms.</p> <p>Conclusion</p> <p>Mutations in the coding regions of the <it>KIT</it> gene appear not to be a common cause of 46,XX spontaneous premature ovarian failure in North American women.</p>