20.500.12556/RUL-164306 Genetska heterogenost pri otrocih z amelogenesis imperfecta v Sloveniji in njen vpliv na rentgensko določljivo morfologijo zob doktorska disertacija Genetic heterogeneity in children with amelogenesis imperfecta in Slovenia and its influence on X-ray detectable tooth morphology doctoral dissertation Amelogenesis imperfecta (AI) je heterogena skupina dednih bolezni s kliničnimi znaki razvojno okvarjene zobne sklenine. V raziskavi smo analizirali eksom pri 24 slovenskih otrocih z nesindromskimi oblikami AI in skušali opredelili genetsko etiologijo v genih znano povezanih z AI. Nadalje smo z uporabo programa Fiji ImageJ analizirali ortopantomogramske posnetke (OPT) otrok z AI in OPT posnetke otrok v kontrolni skupini ter določili tri rentgenske parametre: skleninski kot (SK), dentinski kot (DK) ter razmerje mineralizacije sklenine in dentina (RM), s katerimi smo kvantitativno vrednotili spremenjeno sklenino neizraslih drugih spodnjih stalnih kočnikov. V 13 družinah smo opredelili patološke različice v treh genih znano povezanih z AI: v osmih družinah (61,5 %) v genu ENAM, v treh družinah (23,1 %) v genu AMELX in v dveh družinah (15,4 %) v genu MMP20. Od teh je bilo pet različic novih. Na podlagi rezultatov kontrolne skupine smo neodvisno izračunali mejne vrednosti SK, DK in RM, določili območje hipomineralizacije in hipoplazije ter prikazali odstopanja v količini in kakovosti sklenine z visoko ponovljivostjo. Primerjava povezanosti vseh treh rentgenskih parametrov skupaj (SK, DK in RM), kot tudi posamično za DK in RM, je bila, glede na opredeljene patološke različice v treh genih znano povezanih z AI, statistično značilna. Z analizo modela smo ocenili vpliv vseh treh rentgenskih parametrov skupaj na prisotnost patoloških različic v treh genih znano povezanih z AI, z 90 % (84,0 – 98,0 %) AUC-napovedno močjo. V raziskavi smo predstavili potencial preprostega orodja za natančnejše prepoznavanje značilnosti razvojno okvarjene sklenine, s katerim bi lahko izboljšali diagnostiko AI. Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders affecting dental enamel. In this research, we analysed the exomes of 24 Slovenian children with non-syndromic forms of AI to identify the genetic etiology in AI-related genes. Additionally, using the Fiji ImageJ programme, we analysed the panoramic radiographs (OPTs) of children with AI and those in a control group. We determined three radiographic parameters: enamel angle (EA), dentin angle (DA), and enamel/dentin mineralisation ratio (EDMR), to quantitatively evaluate changes in the enamel of second lower permanent molar buds. In 13 families we identified pathological variants in three AI-related genes: eight families (61.5%) had variants in the ENAM gene, three families (23.1%) in the AMELX gene, and two families (15.4%) in the MMP20 gene. Among these, five variants were novel. Based on the results the control group, we independently calculated the cut-off values for EA, DA, and EDMR. Hypomineralization and hypoplastic regions were observed, indicating significant deviations in enamel quantity and quality with high reproducibility. The correlation of all three parameters, as well as individually for DA and EDMR, was statistically significant based on the identified pathological variants. Assessing the influence of all three parameters on the presence of pathological variants in three AI-related genes yielded a 90% (84.0 – 98.0%) AUC-estimated predictive power using the random forest model. This research highlights the potential of a novel interpretive tool in diagnosing developmental enamel defects, offering insights into the genetic basis and radiographic features of AI. Amelogenesis imperfecta razvojno okvarjena sklenina genetska analiza rentgenska analiza neizrasli drugi spodnji stalni kočniki novo interpretativno orodje Amelogenesis imperfecta developmentally defective enamel molecular genetic analysis radiographic analysis lower second permanent molar buds new evaluation tool true false false Slovenski jezik Angleški jezik Doktorsko delo/naloga 2024-10-21 12:37:29 2024-10-21 12:37:41 2024-11-07 13:17:00 0000-00-00 00:00:00 2024 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 28576 214071043 5706.pdf 5706.pdf 1 53A5BB9F52B5F825B9932CD92E0E3F48 de768674e9bc614103df71cc54391820bac30d0cdbe9df70df095672c73cfb6e 380e1a44-8f98-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=194614 Biotehniška fakulteta 0 0 0