Obstetrics and GynecologyObstetrics and GynecologyАкушерство и гинекология0300-90922412-5679Bionika Media246776ArticlesСтатьиReview ArticleDETERMINATION OF FREE EMBRYONIC DNA IN THE PLASMA OF PREGNANT WOMEN FOR NONINVASIVE PRENATAL GENETIC DIAGNOSISОПРЕДЕЛЕНИЕ СВОБОДНОЙ ЭМБРИОНАЛЬНОЙ ДНК В ПЛАЗМЕ КРОВИ БЕРЕМЕННЫХ ДЛЯ НЕИНВАЗИВНОЙ ПРЕНАТАЛЬНОЙ ГЕНЕТИЧЕСКОЙ ДИАГНОСТИКИTETRUASHVILIN. KТЕТРУАШВИЛИНана Картлосовна

доктор медицинских наук, профессор, руководитель 2-го отделения акушерского патологии беременности

tetrauly@mail.ruFEDOROVAN. IФЕДОРОВАНаталья Игоревна

врач 2-го отделения акушерского патологии беременности

natasha_fedorova@mail.ruFAIZULLINL. ZФАЙЗУЛЛИНЛеонид Закиевич

кандидат биологических наук, ведущий научный сотрудник лаборатории молекулярно-генетических методов

lfaizullin@mail.ruKARNAUKHOVV. NКАРНАУХОВВиталий Николаевич

младший научный сотрудник лаборатории молекулярно-генетических методов

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of RussiaФГБУ Научный центр акушерства, гинекологии и перинатологии им. академика В.И. Кулакова Минздравсоцразвития России150620126NO6 (2012)№6 (2012)4817022023Copyright ©; 2012, Bionika MediaCopyright ©; 2012, ООО «Бионика Медиа»2012Bionika MediaООО «Бионика Медиа»https://journals.eco-vector.com/0300-9092/article/view/246776

The need for timely diagnosis with the minimum risk to mother and fetus determines whether it is urgent to make a noninvasive prenatal diagnosis. The detection of free (extracellular) embryonic DNA circulating in the maternal plasma has opened up fresh opportunities for the noninvasive genetic diagnosis of the fetus and the state of pregnancy. Embryonic DNA may be detected at 5—6 weeks’ gestation and promptly disappears after childbirth. Current molecular biological technologies to investigate this DNA make it possible to predict pregnancy complications, to define fetal sex and rhesus, and to diagnose gene and chromosomal mutations.

Необходимость своевременной постановки диагноза с минимальным риском для матери и плода определяет актуальность неинвазивной пренатальной диагностики. Выявление свободной (внеклеточной) эмбриональной ДНК, циркулирующей в плазме крови матери, открыло новые возможности неинвазивной генетической диагностики плода и состояния беременности. Эмбриональная ДНК может быть обнаружена на 5—6 нед гестации и быстро исчезает после родов. Современные молекулярно-биологические технологии исследования этой ДНК позволяют прогнозировать осложнения беременности, определять пол и резус-фактор плода, диагностировать генные и хромосомные мутации.

free embryonic DNApregnancyrhesus factoraneuploidyсвободная эмбриональная ДНКбеременностьрезус-факторанеуплоидияAlberry M., Maddocks D., Jones M. et al. Free fetal DNA in maternal plasma in anembryonic pregnancies: confirmation that the origin is the trophoblasts // Prenat. Diagn. - 2007. -Vol. 27. - P. 415-418.Avent N.D., Reid M.E. The Rh blood group system: a review // Blood. - 2000. - Vol. 95. - P. 375 - 387.Avent N.D. RhD genotyping from maternal plasma: guidelines and technical challenges // Methods Mol. Biol. - 2008. - Vol. 444. - P. 185 -201.Bianchi D.W., Zickwolf G.K., Weil G.J. et al. Male fetal progenitor cells persistin maternal blood for as long as 27 years postpartum // Proc. Nat. Acad. Sci USA. - 1996. -Vol. 93. - P. 705 -708.Chan K.C.A., Zhang J., Hui A.B. et al. Size distributions of maternal and fetal DNA in maternal plasma // Clin. Chem. -2004. - Vol. 50. - P. 88-92.Costa J.M., Benachi A., Gautier E. New strategy for prenatal diagnosis of X-linked disorders // N. Engl. J. Med. - 2002. -Vol. 346. - P. 1502.Chiu R.W.K., Lau T.K., Cheung P.T. et al. Noninvasive prenatal exclusion of congenital adrenal hyperplasia by maternal plasma analysis: a feasibility study // Clin. Chem. - 2002. - Vol. 48. - P. 778-780.Di Renzo G.C., Rosati A., Sarti R.D. et al. Does fetal sex affect pregnancy outcome? // Gend. Med. - 2007. - Vol. 4. -P. 19-30.Dhallan R., Guo X., Emche S. et al. A non-invasive test for prenatal diagnosis based on fetal DNA present in maternal blood: a preliminary study // Lancet. - 2007. - Vol. 10. -P. 474-481.Finning K.M., Chitty L.S. Non-invasive fetal sex determination: impact on clinical practice // Semin. Fetal. Neonatal Med. - 2008. - Vol. 13. - P. 69-75.Fan H.C., Blumenfeld Y.J., Chitkara U. et al. Analysis of the Size Distributions of Fetal and Maternal Cell-Free DNA by Paired-End Sequencing // Clin. Chem. - 2010. - Vol. 5. -P. 1279-1286.Finning K., Martin P., Summers J. et al. Effect of high throughput RhD typing of fetal DNA in maternal plasma on use of anti-RhD immunoglobulin in RhD negative pregnant women: prospective feasibility study // BMJ. - 2008. -Vol. 12. - P. 816-818.Finning K., Martin P., Daniels G. The use of maternal plasma for prenatal RhD blood group genotyping // Methods Mol. Biol. - 2009. - Vol. 49. - P. 143-157.Farina A., Sekizawa A., Rizzo N. et al. Cell-free fetal DNA (SRY locus) concentration in maternal plasma is directly correlated to the time elapsed from the onset of PET to the collection of blood // Prenat. Diagn. - 2004. - Vol. 24. -P. 293-297.Geifman-Holtzman O., Ober Berman J. Prenatal diagnosis: update on invasive versus noninvasive fetal diagnostic testing from maternal blood // Expert. Rev. Mol. Diagn. - 2008. -Vol. 8, № 6. - P. 727-751.Human Genetics Commission. Choosing the future: genetics and reproductive decision making. July 2004.Hill M., Finning K., Martin P. et al. Non-invasive prenatal determination of fetal sex: translating research into clinical practice // Clin. Genet. - 2010. - Aug 19.Hill M., Taffinder S., Chitty L.S. et al. Incremental cost of non-invasive prenatal diagnosis versus invasive prenatal diagnosis of fetal sex in England // Prenat. Diagn. - 2011. -Vol. 31, № 3. - P. 267 - 255.Hall A., Bostanci A., Wright C.F. Non-invasive prenatal diagnosis using cell-free fetal DNA technology: applications and implications // Public Health Genomics. - 2010. -Vol. 13, № 4. - P. 246-255.Hung E.C., Chiu R.W., Lo Y.M. Detection of circulating fetal nucleic acids: a review of methods and applications // J. Clin. Pathol. - 2009. - Vol. 62, № 4. - P. 308-313.Illanes S., Parra M., Serra R. et al. Increased free fetal DNA levels in early pregnancy plasma of women who subsequently develop preeclampsia and intrauterine growth restriction // Prenat. Diagn. - 2009. - Vol. 29, № 12. -P. 1118-1122.Ishihara N., Matsuo H., Murakoshi H. et al. Increased apoptosis in the syncytiotrophoblast in human term placentas complicated by either PET or intrauterine growth retardation // Am. J Obstet. Gynecol. - 2002. - Vol. 86, № 1. -P. 158-166.Leung T.N., Lau T.K., Chung T.K. Thalassaemia screening in pregnancy // Curr. Opin. Obstet. Gynecol. - 2005. - Vol. 17, № 2. - P. 129-134.Leung T.N., Zhang J., Lau T.K. et al. Increased maternal plasma fetal DNA concentrations in women who eventually develop PET // Clin. Chem. - 2001. - Vol. 47. - P. 137-139.Lo Y.M., Leung T.N., Tein M.S. et al. Quantitative abnormalities of fetal DNA in maternal serum in preeclampsia // Clin. Chem. - 1999. - Vol. 45, № 2. - P. 184-188.Lo Y.M. Noninvasive prenatal detection of fetal chromosomal aneuploidies by maternal plasma nucleic acid analysis: a review of the current state of the art // BJOG. - 2009. -Vol. 116, № 2. - P. 152-157.Lo Y.M.D., Corbetta N., Chamberlain P.F. et al. Presence of fetal DNA in maternal plasma and serum // Lancet. - 1997 -Vol. 350. - P. 485-487.Lo Y.M.D., Tein M.S., Lau T.K. et al. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis // Am. J. Hum. Genet. -1998. - Vol. 62. - P. 768-775.Masuzaki H., Miura K., Yoshiura K. et al. Detection of cell free placental DNA in maternal plasma: direct evidence from three cases of confined placental mosaicism // J. Med. Genet. - 2004. - Vol. 41. - P. 289 - 292.Melamed N., Yogev Y., Glezerman M. Fetal gender and pregnancy outcome // J. Matern. Fetal. Neonatal Med. -2010. - Vol. 23, № 4. - P. 338-344.Mujezinovic F., Alfirevic Z. Procedure-related complications of amniocentesis and chorionic villous sampling: a systematic review // Obstet. Gynecol. - 2007. - Vol. 110, № 3. -P. 687-694.Masuzaki H., Miura K., Yoshiura et al. Detection of cell free placental DNA in maternal plasma: direct evidence from three cases of confined placental mosaicism // J. Med. Genet. - 2004. - Vol. 41. - P. 289 - 292.Pilgrim H., Lloyd-Jones M., Rees A. Routine antenatal anti-D prophylaxis for RhD-negative women: a systematic review and economic evaluation // Health Techno l. Assess. - 2009. - Vol. 13, № 10. - P. 100-103.Ren C.C., Miao X.H., Cheng H. et al. Detection of fetal sex in the peripheral blood of pregnant women // Fetal. Diagn. Ther. - 2007. - Vol. 22, № 5. - P. 377-382.Rijnders R.J., van der Luijt R.B., Peters E.D. et al. Earliest gestational age for fetal sexing in cell-free maternal plasma // Prenat. Diagn. - 2003. - Vol. 23. -P. 1042-1044.Schmorl G. Pathologische-anatomische Untersuchungen uber Puerperal-Eklampsie. Leipzig: Vogel 1893.Sifakis S., Zaravinos A., Maiz N. et al. First-trimester maternal plasma cell-free fetal DNA and preeclampsia // Am. J. Obstet. Gynecol. - 2009. - Vol. 201, № 5. - P. 472-477.Timmerman E., Pajkrt E., Bilardo C.M. Male gender as a favorable prognostic factor in pregnancies with enlarged nuchal translucency // Ultrasound Obstet. Gynecol. - 2009. - Vol. 34, № 4. - P. 373-378.Tong Y.K., Chiu R.W., Leung T.Y. et al. Detection of restriction enzyme-digested target DNA by PCR amplification using a stem-loop primer: application to the detection of hypomethylated fetal DNA in maternal plasma // Clin. Chem. - 2007. - Vol. 53, № 11. - P. 1906-1914.Wataganara T., Gratacos E., Jani J. et al. Persistent elevation of cell-free fetal DNA levels in maternal plasma after selective laser coagulation of chorionic plate anastomoses in severe midgestational twintwin transfusion syndrome // Am. J. Obstet. Gynecol. - 2005. - Vol. 192. -P. 604-609.Wright C.F., Burton H. The use of cell-free fetal nucleic acids in maternal blood for non-invasive prenatal diagnosis // Hum. Reprod. Update. - 2009. - Vol. 5, № 1. - P. 139-151.Zhong X.Y., Holzgreve W., Hahn S. The levels of circulatory cell free fetal DNA in maternal plasma are elevated prior to the onset of PET // Hypertens Pregnancy. - 2002. -Vol. 21. - P. 77-83.Zhong X.Y., Laivuori H., Livingston J.C. et al. Elevation of both maternal and fetal extracellular circulating deoxyribonucleic acid concentrations in the plasma of pregnant women with PET // Am. J. Obstet. Gynecol. - 2001. - Vol. 184. -P. 414-419.