Molekularno citogenetička analiza sindroma nastalih zbog poremećaja genomskog utiska

master's thesis

• Title (english): Molecular cytogenetics of syndromes caused by genomic imprinting disorders
• Author: Nina Zečević
• Mentor: Kristina Crkvenac Gornik (mentor)
• Mentor: Zorana Grubić (komentor)
• Committee member: Zorana Grubić (predsjednik povjerenstva)
• Committee member: Mirjana Pavlica (član povjerenstva)
• Committee member: Nada Oršolić (član povjerenstva)
• Committee member: Petra Korać (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2024-07-19, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Metilacijski specifična metoda višestrukog umnažanja vezanih proba (MS-MLPA) omogućava
preciznu dijagnostiku malformacijskih sindroma uzrokovanih genomskim utiskivanjem, a to su
sindrom Prader-Willi (PWS), sindrom Angelman (AS), sindrom Beckwith-Wiedemann (BWS) i
sindrom Russell-Silver (RSS). Molekularna podloga i klinička prezentacija navedenih sindroma
vrlo je različita, a fenotipske razlike nastaju zbog različitog genetičkog mehanizma njihovog
nastanka. Cilj ovog istraživanja bio je analizirati broj kopija i metilacijski status utisnutih gena
smještenih u regiji PWS/AS (15q11-q13) i regiji BWS/RSS (11p15.5, 7q32, 7p12 i 14q32) te za
svakog ispitanika napraviti usporedbu fenotipa ovisno o molekularnom genetičkom mehanizmu
nastanka bolesti i potvrdi uputne dijagnoze. Istraživanje je obuhvatilo 104 nesrodna ispitanika
poslanih na dijagnostiku na Odjelu za pedijatriju KBC-a Zagreb. Primjenom metode MS-MLPA
genetički uzrok za PWS određen je kod 37% bolesnika, za AS kod 44%, dok je kod 52% bolesnika
potvrđen BWS. Svega 17% bilo je u skupini bolesnika s kliničkom slikom koja ukazuje na RSS.
Nije utvrđena statistički značajna razlika fenotipova ovisno o molekularnom uzroku nastanka
bolesti kod PWS-a i RSS-a. Između fenotipova potvrđenih i nepotvrđenih bolesnika metodom
MS-MLPA također ne postoji statistički značajna razlika. Ovim istraživanjem je potvrđena
hipoteza da rano otkrivanje genetičke etiologije sindroma nastalih zbog poremećaja genomskog
utiskivanja primjenom tehnika molekularne citogenetike omogućuje bolje predviđanje fenotipa
bolesnika u svrhu pružanja učinkovite individualne terapije.

Abstract (english)

The methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) method
enables precise diagnosis of congenital syndromes caused by genomic imprinting, including
Prader-Willi syndrome (PWS), Angelman syndrome (AS), Beckwith-Wiedemann syndrome
(BWS) and Russell-Silver syndrome (RSS). The molecular etiology and clinical presentation of
these syndromes varies significantly with phenotypic differences arising from distinct genetic
mechanisms. The aim of this study was to analyze the copy number and methylation status of
imprinted genes located in the PWS/AS region (15q11-q13) and the BWS/RSS region (11p15.5,
7q32, 7p12, and 14q32) and to compare the phenotypes of each patient based on the molecular
mechanism of the disease and confirmation of the initial diagnosis. The study included 104
unrelated patients referred for diagnostics to the Department of Pediatrics at UHC Zagreb. The
genetic cause for PWS was identified in 37% of patients, for AS in 44% and for BWS in 52% of
patients. The lowest confirmation rate (17%) was in the group of patients with a clinical
presentation indicative of RSS. No statistically significant difference in phenotypes was found
based on the molecular cause of the disease for PWS and RSS. Additionally, there was no
statistically significant difference between the phenotypes of patients confirmed and not confirmed
by the MS-MLPA method. This study supports the hypothesis that an early identification of the
genetic etiology of syndromes caused by the genomic imprinting disorders using molecular
cytogenetic techniques allows for better prediction of patient phenotypes, enabling thus a more
effective individualized therapy.

• Keywords: delecija; uniparentalna disomija; metoda MS-MLPA; metilacijski status; fenotip
• Keywords (english): deletion; uniparental disomy; MS-MLPA method; methylation status; phenotype
• Language: croatian
• URN:NBN: urn:nbn:hr:217:530758
• Study programme: Title: Experimental Biology-University graduate programme; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra eksperimentalne biologije (sveučilišni/a magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-07-29 11:15:31