{"id":1025,"date":"2017-04-07T13:42:43","date_gmt":"2017-04-07T11:42:43","guid":{"rendered":"http:\/\/www.newslab.sk\/2017\/04\/07\/nestandardne-vysledky-neinvazivneho-prenatalneho-testu-na-chromozomove-poruchy-plodu-mozu-poskytovat-doplnujucu-informaciu-o-zdravotnom-stave-tehotnych-zien\/"},"modified":"2017-10-03T09:11:10","modified_gmt":"2017-10-03T07:11:10","slug":"non-standard-results-of-non-invasive-prenatal-testing-of-chromosomal-fetal-disorders-may-provide-additional-information-about-health-of-pregnant-women","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/non-standard-results-of-non-invasive-prenatal-testing-of-chromosomal-fetal-disorders-may-provide-additional-information-about-health-of-pregnant-women\/","title":{"rendered":"Non-standard results of non-invasive prenatal testing of chromosomal fetal disorders may provide additional information about health of pregnant women"},"content":{"rendered":"<pre><strong><span style=\"color: #ff0000;\">*V\u0161etky tabu\u013eky, grafy a obr\u00e1zky, ktor\u00e9 s\u00fa s\u00fa\u010das\u0165ou \u010dl\u00e1nku, n\u00e1jdete v prilo\u017eenom \r\nPDF s\u00fabore na konci \u0161t\u00fadie.\r\n\r\n\r\n<\/span><\/strong><\/pre>\n<p><strong>\u00davod<\/strong><\/p>\n<p>V roku 1997 \u00a0bola v perif\u00e9rnej \u00a0krvi tehotn\u00fdch \u017eien objaven\u00e1 vo\u013en\u00e1 DNA poch\u00e1dzaj\u00faca z plodu(1). T\u00e1to DNA v\u0161ak nie je priamo uvo\u013e\u0148ovan\u00e1 plodom, ale bunkami cytotrofoblastu placenty, ktor\u00e9 odumr\u00fa v procese apopt\u00f3zy(2). NIPT predstavuje pokro\u010dil\u00fd skr\u00edningov\u00fd test, nie v\u0161ak diagnostick\u00fd test, preto\u017ee m\u00f4\u017ee \u00a0vies\u0165 k falo\u0161ne pozit\u00edvnym \u00a0alebo \u00a0menej \u010dasto k falo\u0161ne negat\u00edvnym v\u00fdsledkom. Pr\u00e1ve \u00a0placent\u00e1rny p\u00f4vod \u00a0a fenom\u00e9n placent\u00e1rneho mozaicizmu zodpovedaj\u00fa za mal\u00fa mieru diskordantn\u00fdch v\u00fdsledkov NIPT a skuto\u010dn\u00e9ho karyotypu plodu a s\u00fa\u00a0 jednou \u00a0z biologick\u00fdch pr\u00ed\u010din nespr\u00e1vneho v\u00fdsledku NIPT(3). \u010eal\u0161ou z pr\u00ed\u010din falo\u0161ne pozit\u00edvnych v\u00fdsledkov NIPT je syndr\u00f3m mizn\u00faceho dvoj\u010da\u0165a, preto\u017ee u mizn\u00faceho dvoj\u010da\u0165a je vy\u0161\u0161\u00ed v\u00fdskyt aneuploidi\u00ed a pr\u00edslu\u0161n\u00e1 \u010das\u0165 placenty uvo\u013e\u0148uje aberantn\u00fa DNA(11). N\u00edzky podiel DNA plodu (menej \u00a0ako 4 %) m\u00f4\u017ee \u00a0by\u0165 pr\u00ed\u010dinou falo\u0161ne negat\u00edvneho v\u00fdsledku. DNA z\u00edskan\u00e1 z plazmy \u00a0je zmesou dominuj\u00facej materskej DNA a DNA plodu, ktor\u00e1 predstavuje priemerne len okolo 10 \u2013 20 % medzi 10. a 21. t\u00fd\u017ed\u0148om tehotenstva(4). V\u00fdsledok \u00a0NIPT m\u00f4\u017ee by\u0165 preto \u00a0ovplyvnen\u00fd \u00a0aj aberantn\u00fdm genotypom matky (na- pr. mozaicizmus). A\u017e v roku 2008 \u00a0bola \u00a0prv\u00fdkr\u00e1t \u00a0publikovan\u00e1\u00a0 nov\u00e1 \u00a0met\u00f3da analyzuj\u00faca cirkuluj\u00facu \u00a0DNA v krvi tehotnej \u00a0pomocou sekven\u00e1torov novej \u00a0gener\u00e1cie, v\u010faka \u00a0ktorej bolo mo\u017en\u00e9 s vysokou \u00a0spo\u013eahlivos\u0165ou odl\u00ed\u0161i\u0165 trizomick\u00e9 plody od euploidn\u00fdch(5). Bol zalo\u017een\u00fd na celogen\u00f3movom sekvenovan\u00ed vo\u013enej cirkuluj\u00facej \u00a0DNA, priraden\u00ed \u00a0sekvenci\u00ed k jednotliv\u00fdm chromoz\u00f3mom a n\u00e1sledn\u00e9mu porovnaniu pomerov sledovan\u00fdch a referen\u010dn\u00fdch chromoz\u00f3mov s pomermi zisten\u00fdmi pre s\u00fapravu vzoriek euploidn\u00fdch tehotenstiev. Prv\u00fd komer\u010dne dostupn\u00fd NIPT test pri\u0161iel v roku 2011 a odvtedy do\u0161lo k ve\u013ek\u00e9mu \u00a0n\u00e1rastu po\u010dtu \u00a0vy\u0161etren\u00fdch tehotn\u00fdch, ako\u00a0 aj k dostupnosti r\u00f4znych NIPT(6). Prax uk\u00e1zala pr\u00ednos \u00a0NIPT met\u00f3d vo vysokej citlivosti \u00a0a \u0161pecificity \u010dast\u00fdch chromoz\u00f3mo- v\u00fdch por\u00fach plodu v porovnan\u00ed so \u0161tandardn\u00fdm skr\u00edningom a NIPT predstavuje najspo\u013eahlivej\u0161iu met\u00f3du v pr\u00edpade, \u017ee tehotn\u00e1 nie je ochotn\u00e1 podst\u00fapi\u0165 amniocent\u00e9zu(7).<\/p>\n<p>NIPT testy \u00a0v\u0161ak nes\u00fa predov\u0161etk\u00fdm genomick\u00fa inform\u00e1ciu o tehotnej \u017eene. \u00a0Pr\u00e1ca Bianchi a kol.(7) poukazuje na zachytenie e\u0161te \u00a0neidentifikovan\u00fdch desiatich pr\u00edpadov materskej malignity u tehotn\u00fdch \u017eien v r\u00e1mci \u00a0poskytovania komer\u010dn\u00e9ho NIPT testu, \u00a0ktor\u00e9\u00a0 boli pri n\u00e1slednom klinickom mana\u017emente aj potvrden\u00e9. Mal\u00edgne \u00a0bunky \u00a0toti\u017e do \u00a0obehu uvo\u013e\u0148uj\u00fa DNA podobne ako placenta, pri\u010dom \u00a0tumorov\u00e9 tkanivo je \u010dasto tvoren\u00e9 bunkami s viacpo\u010detn\u00fdmi chromoz\u00f3mov\u00fdmi \u00a0aber\u00e1ciami. Malignita \u00a0v\u0161ak \u00a0nie je jedinou mo\u017enou pr\u00ed\u010dinou \u00a0zachytenia abnorm\u00e1lneho NIPT chromoz\u00f3mov\u00e9ho profilu. Chan a spol.(8) v roku 2015 pouk\u00e1zali na to \u017ee aj syst\u00e9mov\u00fd \u00a0lupus \u00a0erythematosus (SLE) sp\u00f4sobuje viacpo\u010detn\u00e9 \u00a0aberantn\u00e9 chromoz\u00f3mov\u00e9 artefakty pri celogen\u00f3movej anal\u00fdze DNA z placenty. T\u00e1to pr\u00e1ca poukazuje na zachyten\u00fd pr\u00edpad \u00a0tehotnej s pr\u00edtomn\u00fdmi viacpo\u010detn\u00fdmi chromoz\u00f3mov\u00fdmi aber\u00e1ciami zisten\u00fdmi pomocou NIPT testu(9) s rozborom mo\u017en\u00fdch pr\u00ed\u010din. Pr\u00e1ve \u00a0schopnos\u0165 zachyti\u0165 in\u00e9 aber\u00e1cie okrem \u00a0testovan\u00fdch vn\u00edmame ako\u00a0 hlavn\u00fa v\u00fdhodu celogen\u00f3mov\u00e9ho pr\u00edstupu pri NIPT skr\u00edningu.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Materi\u00e1l a met\u00f3dy<\/strong><\/p>\n<p>U pacientky vo veku 32 rokov, po in vitro fertiliz\u00e1cii \u00a0bol indikovan\u00fd \u00a0NIPT test. Odberov\u00e1 sk\u00famavka s perif\u00e9rnou krvou odobratou do EDTA bola prepraven\u00e1 do laborat\u00f3ria a do 24 hod\u00edn \u00a0z nej bola \u00a0z\u00edskan\u00e1 \u010dist\u00e1 frakcia \u00a0plazmy. \u00a0Z plazmy bola\u00a0 izolovan\u00e1 celkov\u00e1 \u00a0DNA pomocou kitu DNA Blood Mini kit (Qiagen, DE) a cel\u00fd v\u00fd\u0165a\u017eok bol pou\u017eit\u00fd \u00a0na pr\u00edpravu fragmentovej sekvena\u010dnej kni\u017enice \u00a0s kitom\u00a0 TruSeq \u00a0Nano (Illumina, USA) na \u00fa\u010dely mas\u00edvne paraleln\u00e9ho sekvenovania na sekven\u00e1tore Illumina MiSeq. Vykonan\u00e9 bolo p\u00e1rov\u00e9 sekvenovanie s d\u013a\u017ekou \u00a0\u010d\u00edtania \u00a075bp. \u00a0Z\u00edskan\u00e9 d\u00e1ta \u00a0zo sekvenovania boli spracovan\u00e9 pomocou bioinformatick\u00e9ho expertn\u00e9ho n\u00e1stroja NIPT-APP, ktor\u00fd zabezpe\u010dil kvalitat\u00edvne filtrovanie d\u00e1t, mapovanie \u010d\u00edtania k referen\u010dn\u00e9mu \u013eudsk\u00e9mu gen\u00f3mu verzie hg19, zisteniu po\u010detnost\u00ed \u010d\u00edtania pre jednotliv\u00e9 chromoz\u00f3my, ako aj pre rovnomern\u00e9 segmenty chromoz\u00f3mov, ktor\u00e9 pomocou vlastn\u00e9ho algoritmu boli porovnan\u00e9 s norm\u00e1lnymi po\u010detnos\u0165ami referen\u010dn\u00fdch vzoriek. \u00a0Na z\u00e1klade porovnania vzoriek s referen\u010dn\u00fdmi hodnotami bolo stanoven\u00e9 Z sk\u00f3re \u00a0pre analyzovan\u00e9 chromoz\u00f3my pomocou vyvinut\u00e9ho algoritmu Multinomial. Na \u00fa\u010dely kontroly validity v\u00fdsledkov boli v\u00fdsledky vizualizovan\u00e9 aj formou grafickej reprezent\u00e1cie chromoz\u00f3mov \u00a0na subchromoz\u00f3movej \u00farovni pomocou n\u00e1stroja Circos(10). Vzh\u013eadom na v\u00fdsledok bol s odstupom dvoch t\u00fd\u017ed\u0148ov vykonan\u00fd opakovan\u00fd odber \u00a0s pou\u017eit\u00edm rovnak\u00e9ho postupu.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>V<\/strong><strong>\u00fdsledky<\/strong><\/p>\n<p>Pri prvej NIPT anal\u00fdze vzorky sme z\u00edskali 6,9 mili\u00f3na p\u00e1rov\u00fdch \u010d\u00edtan\u00ed, ktor\u00e9 \u00a0sa unik\u00e1tne mapovali na gen\u00f3m vo verzii GRCh37. Bola zisten\u00e1 pozitivita na triz\u00f3miu chromoz\u00f3mu 18 (Z sk\u00f3re \u00a0&gt; 6) a z\u00e1rove\u0148 hodnoty Z sk\u00f3re chromoz\u00f3mov 21 a 13 boli v sivom \u00a0p\u00e1sme (Z sk\u00f3re \u00a0medzi \u00a02,5 a 4), \u010do je ne\u0161tandardn\u00e9 <strong><em>(obr\u00e1zok 1)<\/em><\/strong>. V\u00fdsledok \u00a0po 2. odbere bol rovnak\u00fd. Pomocou n\u00e1stroja Circos sme hodnotili distrib\u00faciu \u010d\u00edtania v r\u00e1mci \u00a0v\u0161etk\u00fdch autoz\u00f3mov <strong><em>(obr\u00e1zok 2)<\/em><\/strong>. Pozorovali sme pr\u00edtomnos\u0165 viacpo\u010detn\u00fdch subchromoz\u00f3mov\u00fdch aber\u00e1ci\u00ed (mikrodel\u00e9cie a duplik\u00e1cie) na ka\u017edom z chromoz\u00f3mov <strong><em>(obr\u00e1zok \u00a01)<\/em><\/strong>. Pacientka bola\u00a0 na z\u00e1klade v\u00fdsledkov \u00a0indikovan\u00e1 na \u00a0amniocent\u00e9zu.<\/p>\n<p><strong>Diskusia a z\u00e1ver<\/strong><\/p>\n<p>Neinvaz\u00edvne prenat\u00e1lne testy v praxi preuk\u00e1zali vysok\u00fa citlivos\u0165 a \u0161pecificitu pri odha\u013eovan\u00ed naj\u010dastej\u0161\u00edch aneuploidi\u00ed plodu \u00a0anal\u00fdzy \u00a0vo\u013enej DNA plodu \u00a0v perif\u00e9rnej \u00a0krvi tehotn\u00fdch \u017eien. Od p\u00f4vodn\u00e9ho n\u00e1zoru expertov na prenat\u00e1lnu starostlivos\u0165 pri vyu\u017eit\u00ed NIPT testu ako alternat\u00edvy \u0161tandardn\u00e9ho skr\u00edningu pre tehotn\u00e9 s vy\u0161\u0161\u00edm \u00a0rizikom plodu s Downov\u00fdm syndr\u00f3mom bada\u0165 \u00a0posun k n\u00e1zoru vhodnosti nasadenia testu ako prvej vo\u013eby skr\u00edningu \u00a0na naj\u010dastej\u0161ie aneuploidie plodu. No skupina testov zalo\u017een\u00fdch na celogen\u00f3movom skenovan\u00ed dok\u00e1\u017ee poskytn\u00fa\u0165 \u00a0dopl\u0148uj\u00face inform\u00e1cie, ktor\u00e9\u00a0 sa t\u00fdkaj\u00fa samotnej tehotnej \u017eeny.<\/p>\n<p>Pri poskytovan\u00ed NIPT testu v na\u0161om laborat\u00f3riu sme zachytili pr\u00edpad tehotnej, ktor\u00e1 mala abnorm\u00e1lny v\u00fdsledok NIPT testu a vo vizualiz\u00e1cii distrib\u00facie \u010d\u00edtania pre v\u0161etky chromoz\u00f3my sme pozorovali ve\u013ek\u00fd po\u010det subchromoz\u00f3mov\u00fdch odch\u00fdlok (duplik\u00e1ci\u00ed aj del\u00e9ci\u00ed). Okultn\u00e1 malignita je jedn\u00fdm z mo\u017en\u00fdch vysvetlen\u00ed \u00a0z\u00edskania tohto \u00a0ne\u0161tandardn\u00e9ho v\u00fdsledku.<\/p>\n<p>Masa mal\u00edgneho tumoru m\u00f4\u017ee \u00a0ma\u0165 v\u0161etky \u00a0alebo subpopul\u00e1cie \u00a0buniek \u00a0s pr\u00edtomn\u00fdmi subchromoz\u00f3mov\u00fdmi aber\u00e1ciami, ktor\u00e9 v d\u00f4sledku poruchy \u00a0v kontroln\u00fdch a opravn\u00fdch mechanizmoch bunky pre\u017e\u00edvaj\u00fa\u00a0 a mno\u017eia sa. Pr\u00e1ve pri rozpade tak\u00fdchto buniek \u00a0sa do \u00a0cirkul\u00e1cie \u00a0uvo\u013e\u0148uj\u00fa aberantn\u00e9 DNA tumoru a menia \u00a0tak relat\u00edvne \u00a0zast\u00fapenie fragmentov v aberantn\u00fdch oblastiach. Viacer\u00e9 \u00a0pr\u00e1ce uv\u00e1dzaj\u00fa zachytenie tak\u00fdchto \u00a0pr\u00edpadov skrytej\u00a0 malignity \u00a0v skorom \u0161t\u00e1diu v r\u00e1mci NIPT, ktor\u00e9 \u00a0boli n\u00e1sledne potvrden\u00e9, lokalizovan\u00e9, pr\u00edpadne aj lie\u010den\u00e9 pri \u010fal\u0161om klinickom mana\u017emente(7).<\/p>\n<p>Pr\u00ed\u010dinou \u00a0zisten\u00e9ho aberantn\u00e9ho profilu v\u0161ak \u00a0m\u00f4\u017ee \u00a0by\u0165 aj SLE a napriek \u00a0zatia\u013e nedostupn\u00fdm inform\u00e1ci\u00e1m z odbornej literat\u00fary \u00a0mo\u017eno predpoklada\u0165, \u017ee aj in\u00e9 autoimunitn\u00e9 ochorenia\u00a0 m\u00f4\u017eu \u00a0sp\u00f4sobi\u0165 podobn\u00fd v\u00fdsledok. \u00a0Pri pozorovan\u00ed abnorm\u00e1lneho profilu je potrebn\u00e9 vyl\u00fa\u010di\u0165 SLE alebo \u00a0in\u00e9 autoimunitn\u00e9 ochorenia u pacientky. V anamn\u00e9ze v\u0161ak pacientka neuviedla SLE.<\/p>\n<p>V analyzovanom pr\u00edpade treba \u00a0vzia\u0165 do \u00favahy aj tretiu alternat\u00edvnu pr\u00ed\u010dinu. Tehotn\u00e1 \u017eena \u00a0toti\u017e podst\u00fapila proced\u00faru in vitro fertiliz\u00e1cie, pri\u010dom boli implantovan\u00e9 dve embry\u00e1, jedno z nich neprosperovalo. Zdrojom aberantnej DNA pozorovanej v NIPT teste by teda \u00a0mohlo by\u0165 aj jedno z embry\u00ed.<\/p>\n<p>Na definit\u00edvne \u00a0stanovenie pr\u00ed\u010diny pozorovan\u00e9ho abnorm\u00e1lneho profilu \u00a0je \u00a0potrebn\u00e9 vykona\u0165 \u00a0dopl\u0148uj\u00face vy\u0161etrenia a z\u00edska\u0165 \u010fal\u0161ie anamnestick\u00e9 \u00fadaje. \u00a0K\u013e\u00fa\u010dov\u00fd je v\u00fdsledok z anal\u00fdzy \u00a0vzorky z\u00edskanej z amniocent\u00e9zy, v\u010faka \u010domu \u00a0bude mo\u017en\u00e9 vyl\u00fa\u010di\u0165 aber\u00e1cie pr\u00edtomn\u00e9 u prosperuj\u00faceho plodu. Vzh\u013eadom \u00a0na odber \u00a0z vn\u00fatra plodov\u00e9ho obalu prosperuj\u00faceho dvoj\u010da\u0165a pravdepodobne nebude mo\u017en\u00e9 zisti\u0165, \u010di aberantn\u00e1 DNA zachyten\u00e1 v perif\u00e9rnej krvi poch\u00e1dza z druh\u00e9ho embrya. Ten v\u0161ak pacientka odmieta. Vzorka placenty z\u00edskan\u00e1 pomocou CVS a jej karyotypov\u00e1 anal\u00fdza by mohla \u00a0by\u0165 vhodnou met\u00f3dou na stanovenie embryon\u00e1lneho p\u00f4vodu aberantnej DNA. Definit\u00edvne\u00a0 v\u0161ak mo\u017eno embryon\u00e1lny p\u00f4vod \u00a0abe- rantnej \u00a0DNA potvrdi\u0165 alebo vyl\u00fa\u010di\u0165 a\u017e po ukon\u010den\u00ed gravidity pod\u013ea vymiznutia aberantn\u00e9ho sign\u00e1lu. Z anamn\u00e9zy pacientky alebo \u0161pecifick\u00fdmi vy\u0161etreniami bude \u00a0mo\u017en\u00e9 preveri\u0165 hypot\u00e9zu o pr\u00edtomnosti SLE. Po vyl\u00fa\u010den\u00ed predch\u00e1dzaj\u00facich pr\u00ed\u010din by bolo potrebn\u00e9 vy\u0161etri\u0165 okultn\u00fa malignitu.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Z\u00e1ver<\/strong><\/p>\n<p>Celogen\u00f3mov\u00fd pr\u00edstup pri neinvaz\u00edvnom testovan\u00ed na naj\u010dastej\u0161ie chromoz\u00f3mov\u00e9 poruchy \u00a0m\u00f4\u017ee by\u0165 v\u00fdznamn\u00fdm zdrojom inform\u00e1ci\u00ed \u00a0o zdravotnom stave tehotn\u00fdch \u017eien a po- m\u00f4c\u0165\u00a0 tak\u00a0 pri odha\u013eovan\u00ed z\u00e1va\u017en\u00fdch patologick\u00fdch fenom\u00e9nov. Identifikovali sme pr\u00edpad s viacpo\u010detn\u00fdmi chromoz\u00f3mov\u00fdmi aber\u00e1ciami s viacer\u00fdmi \u00a0mo\u017en\u00fdmi pr\u00ed\u010dinami \u00a0vzniku, no na stanovenie ich pr\u00ed\u010diny je potrebn\u00fd vhodn\u00fd algoritmus diferenci\u00e1lnej diagnostiky.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Literat\u00fara<\/strong><br \/>\n1. Lo YM, Corbetta N, et al. Presence of fetal DNA in maternal plasma and serum. Lancet 1997; 350: 485-487.<br \/>\n2. Faas BH, de Ligt J, Janssen I, et al. Non-invasive prenatal diagnosis of fetal aneuploidies using massively parallel sequencing-byligation and evidence that cell-free fetal DNA in the maternal plasma originates from cytotrophoblastic cells. Expert Opin Biol Ther 2012; 12: S19-S26.<br \/>\n3. Grati FR, Malvestiti F, Ferreira JC, et al. Fetoplacental mosaicism: potential implications for false-positive and false-negative noninvasive prenatal screening results. Genet Med 2014; 16(8): 620-4.<br \/>\n4. Taglauer ES, Wilkins-Haug L, Bianchi DW. Review: cell-free fetal DNA in the maternal circulation as an indication of placental health and disease. Placenta 2014; 35: Suppl S64-8.<br \/>\n5. Fan HC, Blumenfeld YJ, Chitkara U, et al. Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc Natl Acad Sci U S A 2008; 105(42): 16266-71.<br \/>\n6. Bianchi DW, Wilkins-Haug L. Integration of Noninvasive DNA Testing for Aneuploidy into Prenatal Care: What Has Happened Since the Rubber Met the Road? Clinical Chemistry 2014; 60(1): 78-87.<br \/>\n7. Bianchi DW, Chudova D, Sehnert AJ, et al. Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies. JAMA 2015; 314(2): 162-169.<br \/>\n8. Chan RWY, Jiang P, Peng Z, et al. Plasma DNA aberrations in systemic lupus erythematosus revealed by genomic and methylomic sequencing. Proc Natl Acad Sci 2015; 111: E5302\u2013E5311.<br \/>\n9. Minarik G, Repiska G, Hyblova M, et al. Utilization of Benchtop Next Generation Sequencing Platforms Ion Torrent PGM and MiSeq in Noninvasive Prenatal Testing for Chromosome 21 Trisomy and Testing of Impact<br \/>\nof In Silico and Physical Size Selection on Its Analytical Performance. PLoS One 2015;10(12): e0144811.<br \/>\n10. Krzywinski M, Schein J, Birol I, et al. Circos: an information aesthetic for comparative genomics. Genome Res 2009; 19(9): 1639-45.<br \/>\n11. Curnow KJ, Wilkins-Haug L, Ryan A, et al. Detection of triploid, molar, and vanishing twin pregnancies by a single-nucleotide polymorphism-based noninvasive prenatal test. Am J Obstet Gynecol 2015; 212(1): 79.e1-9.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>*V\u0161etky tabu\u013eky, grafy a obr\u00e1zky, ktor\u00e9 s\u00fa s\u00fa\u010das\u0165ou \u010dl\u00e1nku, n\u00e1jdete v prilo\u017eenom PDF s\u00fabore na konci \u0161t\u00fadie. \u00davod V roku 1997 \u00a0bola v perif\u00e9rnej \u00a0krvi tehotn\u00fdch \u017eien objaven\u00e1 vo\u013en\u00e1 DNA poch\u00e1dzaj\u00faca z plodu(1). T\u00e1to DNA v\u0161ak nie je priamo uvo\u013e\u0148ovan\u00e1 plodom, ale bunkami cytotrofoblastu placenty, ktor\u00e9 odumr\u00fa v procese apopt\u00f3zy(2). NIPT predstavuje pokro\u010dil\u00fd skr\u00edningov\u00fd test,<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[290],"tags":[379,626,343,625,628,630,629,627],"class_list":["post-1025","post","type-post","status-publish","format-standard","hentry","category-genetics","tag-chromosome-aberrations-en","tag-free-fetal-dna","tag-nipt-en","tag-non-invasive-prenatal-testing","tag-occult-malignity","tag-sle","tag-systemic-lupus-erythematosus","tag-whole-genome-sequencing","typ_clanku-original-work"],"acf":{"abstrakt":"<p>Non-invasive prenatal testing (NIPT) of the most frequent aneuploidies by way of analysing the free DNA obtained from peripheral blood of pregnant women represents on the fastest growing new genetic tests. We first learned of the free fetal DNA present in peripheral plasma of pregnant women in 1997. However, with respect to its small share, it took 14 years for the first test to become available for assessing the most frequent trisomies. Today, several NIPT methods are available applying several methods for detection of changes in the number of monitored chromosomes compared to benchmark chromosomes. The success of NIPT lies in high sensitivity to most frequent types of aberrations, in the case of trisomy 21 it is over 99 % and in the low rate of false positive results. The globally most frequently used tests are based on the analysis comprising the so-called genome-wide approach, while using massive parallel sequencing to analyse the whole DNA collected from peripheral plasma of pregnant women.\u00a0 In 2015, in our laboratory, we implemented a test using the genome-wide approach. It was primarily designed to detect trisomy 21, 18 and 13. However, with a suitable method of data interpretation it is possible to obtain a detailed overview of the status of all chromosomes and detect even small aberrations. Thanks to implementing this NIPT interpretation, we detected a case of a patient in whom we observed multiple sub-chromosomal aberrations on several chromosomes. There are several possible factors that may have caused these changes \u2013 aberrations coming from a vanishing twin, occult malignity as well as systemic lupus erythematosus (SLE). When assessing non-standard NIPT results, it is of key importance to obtain sufficient clinical data to determine the cause. However, genome-wide NIPT can offer also additional information also about the health of the pregnant woman and can represent a valuable tool in prevention and differential diagnostics.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Key words:<\/strong> non-invasive prenatal testing, NIPT, free fetal DNA, chromosome aberrations, whole-genome sequencing, occult malignity, systemic lupus erythematosus, SLE.<\/p>\n","casopis":[{"ID":735,"post_author":"7","post_date":"2017-04-06 13:21:01","post_date_gmt":"2017-04-06 11:21:01","post_content":"<ul>\r\n \t<li>Pseudoglandular nevus \u2013 a rare morphology of melanocytic nevus (case report)<\/li>\r\n \t<li>Differential molecular diagnosis of multiple myeloma and Waldenstr\u00f6m macroglobulinemia<\/li>\r\n \t<li>Molecular analysis of prognostically significant markers of chronic lymphocytic leukemia<\/li>\r\n \t<li>Prevalence of <em>Streptococcus pneumoniae<\/em> phyla in inflammatory diseases of upper airways in preschool age children and their resistance to antibiotics<\/li>\r\n \t<li>Malign melanoma - new aspects of research<\/li>\r\n \t<li style=\"list-style-type: none;\"><\/li>\r\n<\/ul>","post_title":"Newslab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-2017-1","to_ping":"","pinged":"","post_modified":"2017-08-16 21:11:52","post_modified_gmt":"2017-08-16 19:11:52","post_content_filtered":"","post_parent":0,"guid":"http:\/\/www.newslab.sk\/?post_type=casopis&#038;p=735\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"30","upload_clanok":{"ID":1026,"id":1026,"title":"Ne\u0161tandardn\u00e9 v\u00fdsledky neinvaz\u00edvneho prenat\u00e1lneho testu na chromoz\u00f3mov\u00e9 poruchy plodu m\u00f4\u017eu poskytova\u0165 dopl\u0148uj\u00facu inform\u00e1ciu o zdravotnom stave tehotn\u00fdch \u017eien","filename":"Ne\u0161tandardn\u00e9-v\u00fdsledky-neinvaz\u00edvneho-prenat\u00e1lneho-testu-na-chromoz\u00f3mov\u00e9-poruchy-plodu-m\u00f4\u017eu-poskytova\u0165-dopl\u0148uj\u00facu-inform\u00e1ciu-o-zdravotnom-stave-tehotn\u00fdch-\u017eien.pdf","filesize":811503,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2017\/04\/Ne\u0161tandardn\u00e9-v\u00fdsledky-neinvaz\u00edvneho-prenat\u00e1lneho-testu-na-chromoz\u00f3mov\u00e9-poruchy-plodu-m\u00f4\u017eu-poskytova\u0165-dopl\u0148uj\u00facu-inform\u00e1ciu-o-zdravotnom-stave-tehotn\u00fdch-\u017eien.pdf","link":"https:\/\/www.newslab.sk\/en\/non-standard-results-of-non-invasive-prenatal-testing-of-chromosomal-fetal-disorders-may-provide-additional-information-about-health-of-pregnant-women\/nestandardne-vysledky-neinvazivneho-prenatalneho-testu-na-chromozomove-poruchy-plodu-mozu-poskytovat-doplnujucu-informaciu-o-zdravotnom-stave-tehotnych-zien\/","alt":"","author":"7","description":"","caption":"","name":"nestandardne-vysledky-neinvazivneho-prenatalneho-testu-na-chromozomove-poruchy-plodu-mozu-poskytovat-doplnujucu-informaciu-o-zdravotnom-stave-tehotnych-zien","status":"inherit","uploaded_to":1025,"date":"2017-04-07 11:12:02","modified":"2017-04-07 11:12:02","menu_order":0,"mime_type":"application\/pdf","type":"application","subtype":"pdf","icon":"https:\/\/www.newslab.sk\/wp-includes\/images\/media\/document.png"}},"_links":{"self":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1025","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/comments?post=1025"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1025\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1025"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1025"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1025"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}