Prematür over yetersizliği olan hastalarda BMP15 ve FOXL2 geni mutasyon analizi

Prematur over yetersizligi (POY) yuksek FSH duzeylerinin (40 IU/I ve uzeri) eslik ettigi, duzenli menstruel sikluslarin 40 yasindan once 4-6 aydan uzun sure kesilmesi  olarak tanimlanmaktadir.  POY’a neden olabilecek bircok gen tanimlanmistir. Folikulogenez ve folikul rezervinin korunmasindaki rolleri dikkate alindiginda  FOXL2 ve BMP15 genleri bunlarin en onemlileri arasinda yer almaktadir.Bu calisma ile ulkemizdeki POY olgularinda  FOXL2  ve  BMP15  geni  mutasyonlarinin sikligi ve dagiliminin saptanmasi ve bu bilgilere dayanilarak genetik test algoritmasi gelistirmek amaclanmistir.Calismamiza POY on tanisi olan, normal kromozomal kurulusa sahip ve  FMR1  geni premutasyonu tasimayan  79 hasta dahil  edilmis ve bu hastalarda dizi analizi yontemi kullanilarak  FOXL2  ve  BMP15  geni mutasyonlari arastirilmistir.  FOXL2  geninde  % 5,  BMP15  geninde de % 48 oraninda degisiklik saptanmistir. Bu degisiklerden BMP15  c.-9  C>G varyantinin POY ile iliskili oldugu gozlenmis ve bu varyantin POY acisindan onemli bir risk faktoru olabilecegi belirlenmistir. Bu nedenle POY hastalarinda bu varyanta yonelik genetik test uygulanmasi dikkate alinabilir.AbstractPremature ovarian insufficiency (POI) is defined as amenorrhea for at least 4-6 months before the age of 40 together with elevated FSH levels (40 IU/I). Several genes were identified that may cause POI.  FOXL2  and BMP15  are among the most important ones when considering their role in  folliculogenesisand maintenance of follicle reserve. In this study, it was aimed to determine the frequency and distribution of  FOXL2 and BMP15 mutations in patients with POI and, based on this information, to develop genetic test algorithms for POI. Seventy nine patients clinically diagnosed with POI having normal chromosomal constitution with no  FMR1premutation were included in our study and  FOXL2  and  BMP15  mutations were investigated by DNA sequence analysis. The frequency of  FOXL2  and  BMP15  sequence changes were observed as 5 % and 48 %, respectively. Among them, BMP15  c.-9  C>G variant was found to be associated with POI and determined as an important risk factor for POI. Therefore, genetic testing for this variant may be considered in POI patients.