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Prenatal diagnostics of cystic fibrosis by DNA analysis

dc.contributor.advisorSavić, Ana
dc.contributor.otherSretenović, Zoran
dc.contributor.otherGarzičić, Branimir
dc.creatorRadojković, Dragica
dc.date.accessioned2018-12-10T11:45:15Z
dc.date.available2018-12-10T11:45:15Z
dc.date.available2020-07-03T08:06:48Z
dc.date.issued1997
dc.identifier.urihttps://nardus.mpn.gov.rs/handle/123456789/10259
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=6312
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:18973/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=18352399
dc.description.abstractCistična fibroza je najčešće autozomno recesivno oboljenje, koje se u opulaciji belaca javlja saučestalošću od 1/2000 do 1/4000 novorođenčadi. Oboljevaju osobe kod kojih je mutirani CFTR gen prisutan u homozigotnom stanju. S obzirom na težinu ove bolesti. kao i visok rizik za rađanje obolelog deteta (1 :4) kod roditelja koji su heterozigotni nosioci mutiranog gena, prenatalna dijagnostika je od ključnog značaja. U okviru ovog istraživanja analizirano je 105 visokorizičnih porodica, sa ukupno 325 članova. Cilj analiza bio je utvrđivanje informativnosti ovih porodica za dijagnostiku cistične fibroze u narednoj trudnoći. Sprovođena je analiza na prisustvo mutacija u CFFR genu (ΔF508, G542X, G551D, i R553X) bilo direktno, bilo na osnovu polimorfizama dužina restrikcionih fragmenata (RFLP). Ovi podaci su poslužili i za određivanje učestalosti određenih mutacija u našoj populaciji, što je neophodna priprema za genetičko skrinovanje. Od analiziranih porodica 49,5% je bilo informativno, 32,4% poluinformativno, a 18,1% neinformativno za direktnu mutacionu analizu na prisustvo najčešće, ΔF508 mutacije. Od porodica neinformativnih za direktnu mutacionu analizu, 82.9% je bilo potpuno informativno za RFLP analizu. Od analiziranih porodica, 1/3 se javila na prenatalnu dijagnozu u narednoj trudnoći. U ispitivanoj populaciji porodica sa rizikom za rađanje deteta sa cističnom fibrozom, sa barem jednim rođenim obolelim detetom, utvrđeno je da je ΔF508 mutacija zastupljena sa frekvencijom od 67.2%, G542X sa 6.4%, G551D sa 0.6%, dok mutacija R553X nije detektovana. Zbirna učestalost ovih mutacija (73.4%) nije dovoljna za populaciono skrinovanje na mutacije u CFTR genu, u našoj populaciji. Na osnovu sprovedenih istraživanja predlaže se pristup u prenatalnoj dijagnozi i genetičkom savetovanju rizičnih porodica. koji uključuje skrining rizičnih porodica na prisustvo ΔF508 mutacije. Za informativne porodice, preporučuje se prenatalna dijagnoza direktnom detekcijom ove mutacije u narednoj trudnoći. U neinformativnim ili poluinformativnim porodicama sprovodi se RFLP analiza, i porodicama za koje se utvrdi da su informativne preporučuje se prenatalna dijagnoza RFLP analizom u narednoj trudnoći. dok se za neinformativne porodice preporučuje prenatalna dijagnostika ove bolesti određivanjem nivoa mikroviiarnih enzima u amnionskoj tečnosti.sr
dc.description.abstractCystic fibrosis is one of the most common autosomal recessive diseases (from 1 in 2000 to 1 in 4000 live births gives rise to an affected child). Affected persons are homozygous for the mutated CFTR gene. Regarding the severity of this disease, and a high risk (1/4) of couples heterozygous for the mutated gene to have an affected child, it is essential to perform prenatal diagnostics. In this study, 105 (325 members) high risk families were screened for the presence of mutated CFTR gene. The purpose of this study was to detect families informative for diagnostics of cystic fibrosis in further pregnancies. Both direct mutation analysis (for the presence of ΔF508, G542X, G551D and R553X) and indirect molecular genetic analysis for the presence of mutated CFTR gene (RFLPs) were performed. These data gave us too, the frequency of certain mutations in Yugoslav population which is necessary initial step for planning the population genetic screening program. Among analyzed families, 49.5% were fully informative, 32.4% partly informative, and 18.1% noninformative, for direct detection of the most common ΔF508 mutation The rest of the families were analyzed by RFLPs, and 82.9% were fully informative for RFLPs analysis in the next pregnancies. In studied families, at a known risk for cystic fibrosis, having at least one affected child, the frequency of ΔF508 was 67.2%, G542X 6.4%, G551D 0.6%, while R553X was not detected. Cumulative frequency of these mutations (73.4%) is not enough for establishing the population screening program for mutations within CFTR gene in Yugoslav population. As a final result of our study, we propose a proper approach in prenatal diagnosis and genetic counseling in cystic fibrosis in high risk families. The first step is the screening for the ΔF508. For informative families, prenatal diagnosis in the next pregnancy is recommended. In families partly informative or noninformative for the presence of the ΔF508, RFLPs analysis should be performed. In families, informative for RFLPs analysis, the prenatal diagnosis using this method is recommended in the next pregnancies. ln noninformative families, the microvilar enzyme testing inbthe amniotic fluid is the recommended method of prenatal diagnosis of cystic fibrosisen
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Биолошки факултетsr
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjectцистична фиброзаsr
dc.subjectcystic fibrosisen
dc.subjectprenatal diagnosisen
dc.subjectmutation analysisen
dc.subjectпренатална дијагнозаsr
dc.subjectмутациона анализаsr
dc.titlePrenatalna dijagnostika cistične fibroze primenom metoda rekombinantne DNKsr
dc.title.alternativePrenatal diagnostics of cystic fibrosis by DNA analysisen
dc.typedoctoralThesisen
dc.rights.licenseARR
dc.identifier.fulltexthttps://nardus.mpn.gov.rs/bitstream/id/1455/Disertacija.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/1455/Disertacija.pdf
dc.identifier.rcubhttps://hdl.handle.net/21.15107/rcub_nardus_10259


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