Title Bosch-Boonstra-Schaaf Sindrom : diplomski rad
Title (english) Bosch-Boonstra-Schaaf Syndrome
Author Nenad Hrvatin
Mentor Nina Pereza (mentor)
Committee member Saša Ostojić (predsjednik povjerenstva)
Committee member Sanja Dević Pavlić (član povjerenstva)
Committee member Smiljana Ristić (član povjerenstva)
Granter University of Rijeka Faculty of Medicine (Department of Biology and Medical Genetics) Rijeka
Defense date and country 2023-06-21, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Basic Medical Sciences Human Genetics, Genomics and Proteomics
Abstract Svrha ovog diplomskog rada je prikazat rijetku genetičku bolest Bosch-Boonstra-Schaaf sindrom optičke atrofije. Bosch-Boonstra-Schaaf sindrom optičke atrofije je monogenski autosomno dominantni poremećaj NR2F1 gena, karakteriziran zaostajanjem u razvoju, intelektualnim zaostajanjem i optičkom atrofijom. NR2F1 gen se nalazi na dugom kraku 5. kromosoma, na poziciji 5q15. Protein kojeg NR2F1 gen kodira vrši funkciju nuklearnog hormonskog receptora te regulatora transkripcije. Patogene varijante gena i delecije koje zahvaćaju kromosom 5 dovode do pojave kliničke slike Bosch-Boonstra-Schaaf sindroma. Od oftalmoloških kliničkih značajki opisane su abnormalnosti optičkog živca, blijedoća diska i ekskavacija diska, strabizam i latentni nistagmus, a od ostalih značajki opisane su zaostajanje u razvoju i učenju govora, hipotonija, opsesivno kompluzivni poremećaj, oromotorna disfunkcija, repetativni pokreti, značajke iz spektra autizma i poremećaja ponašanja te stanjivanje corpusa callosuma. Najtežu kliničku sliku uzrokuju patogene varijante u DNA vezujućoj domeni proteina, zatim patogene varijante koje uzrokuju prijevremeni stop kodon te frameshift, a nešto blaže kliničke slike uzrokuju potpune delecije gena i patogene varijante u ligand vezujućoj domeni proteina. U većini opisanih slučajeva bolest je nastala de novo, međutim opisana su i dva slučaja gonadnog mozaicizma. Glavni simptomi i znakovi bolesti su hipoplazija optičkog živca ili optička atrofija u kombinaciji sa zaostajanjem u razvoju ili intelektualnom zaostajanju, a konačna dijagnoza postavlja se genetičkim testiranjima. Zbrinjavanje pacijenata usmjereno je na simptome, odnosno na poboljšanje kvalitete života.
Abstract (english) The purpose of this master's thesis is to present a rare genetic disorder called Bosch-Boonstra-Schaaf optic atrophy syndrome. Bosch-Boonstra-Schaaf optic atrophy syndrome is a monogenic autosomal dominant disorder of the NR2F1 gene, characterized by developmental delay, intellectual disability, and optic atrophy. The NR2F1 gene is located on the long arm of chromosome 5, at position 5q15. The protein encoded by the NR2F1 gene functions as a nuclear hormone receptor and transcription regulator. Pathogenic gene variants and deletions affecting chromosome 5 lead to the manifestation of the clinical features of Bosch-Boonstra-Schaaf syndrome. Ophthalmological clinical features include abnormalities of the optic nerve, optic disc pallor and excavation, strabismus and latent nystagmus. Other features include developmental and speech delay, hypotonia, obsessive-compulsive disorder, oromotor dysfunction, repetitive movements, features from the autism spectrum and behavioral disorders, as well as thinning of the corpus callosum. The most severe clinical presentation is caused by pathogenic variants in the DNA-binding domain of the protein, followed by pathogenic variants that result in premature stop codons and frameshift mutations, while complete gene deletions and pathogenic variants in the ligand-binding domain of the protein lead to milder clinical phenotypes. In most described cases, the disease arises de novo, although two cases of gonadal mosaicism have been reported. The main symptoms and signs of the disease are hypoplasia of the optic nerve or optic atrophy combined with developmental delay or intellectual disability, and the final diagnosis is established through genetic testing. Patient management is focused on addressing the symptoms and improving the quality of life.
Keywords
Bosch-Boonstra-Schaaf sindrom
optička atrofija
klinička genetika
Keywords (english)
Bosch-Boonstra-Schaaf syndrome
optic atrophy
clinical genetics
Language croatian
URN:NBN urn:nbn:hr:184:036691
Study programme Title: Medicine Study programme type: university Study level: integrated undergraduate and graduate Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
Type of resource Text
File origin Born digital
Access conditions Open access
Terms of use
Created on 2023-07-02 19:45:43