| Abstract | Uniparentna disomija (UPD) je stanje u kojem homologni par kromosoma u cijelosti ili samo djelomično potječu od jednog roditelja. Dalje se UPD-ovi dijele na izodisomije i heterodisomije. UPD-om se mogu prenijeti autosomno recesivne (AR) bolesti čak i ako je samo jedan roditelj nosioc te ako se radi o UPD-u kromosoma 6, 7, 11, 14, 15 ili 20, mogu nastati određeni sindromi koji su posljedica poremećaja genomskog upisa. Genomski upis je epigenetički mehanizam koji dopušta ekspresiju određenih gena ovisno o roditeljskom podrijetlu. Poremećaj genomskog upisa stvara disbalans među upisanim genima koji je posljedica pretjerane aktivacije ili pretjerane inaktivacije određenih gena. Na taj način nastaju sindromi UPD-ova. Prader-Willi sindrom (PWS) i Angelman sindrom (AS) nastaju zbog poremećaja genomskog upisa 15q11.2-q13 domene. Ako su zbog poremećaja genomskog upisa očevi geni utišani, onda nastaje PWS, a ako su utišani geni majčinoga podrijetla nastaje AS. Glavne karakteristike PWS-a su novorođenačka hipotonija, pretilost i prekomjerno jedenje, zaostajanje u rastu i razvoju, i hipogonadotropni hipogonadizam. Karakteristike AS-a su zastoj u razvoju, teško oštećenje govora, poremećaj ravnoteže i tipično ponašanje u smislu pretjeranoga smijanja i napadaja smijeha. Poremećaji genomskog upisa na kromosomu 11p15 uzrokuju Beckwith-Wiedemann sindrom (BWS) i Silver-Russell sindrom (SRS). Ako se inaktiviraju majčini geni, nastaje BWS, a SRS nastaje ako se inaktiviraju očevi geni. Temple sindrom (TS) i Kagami-Ogata sindrom (KOS) nastaju zbog poremećaja genomskog upisa 14q32 domene. TS nastaje zbog inaktivacije očevih gena, a KOS zbog inaktivacije majčinih gena. BWS i KOS su povezani s prekomjernim rastom organizma i omfalokelom, a BWS je još udružen i s povećanim rizikom za nastanak embrionalnih tumora. SRS i TS povezani su s niskom porođajnom masom, niskim rastom, trokutastim oblikom lica i klinodaktilijom, ali postoje međusobne razlike. Cilj rada je opisati mehanizme nastanka UPD-ova, važnost genomskog upisa te dati pregled važnijih sindroma UPD-ova. |
| Abstract (english) | Uniparental disomy (UPD) is a condition in which a homologous pair of chromosomes is wholly or partially derived from one parent. Further, UPD is divided into isodisomy and heterodisomy. UPD can be the cause of autosomal recessive (AR) diseases even if only one parent is a carrier, and if UPD of chromosomes 6, 7, 11, 14, 15 or 20 is present, certain syndromes can arise that are the result of gene imprinting disorders. Gene imprinting is an epigenetic mechanism that allows the expression of certain genes depending on parental origin. A disorder of gene imprinting creates an imbalance between the genes that are imprinted, which is the result of excessive activation or excessive inactivation of certain genes. In this way, UPD syndromes arise. Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are caused by disruption of the gene imprinting of the 15q11.2-q13 domain. If the paternal genes are silenced, then PWS occurs, and if genes of maternal origin are silenced, AS occurs. The main characteristics of PWS are neonatal hypotonia, obesity and overeating, short stature and hypogonadotropic hypogonadism. AS is characterized by developmental delay, severe speech impairment, balance disorder and typical behavior in terms of excessive laughing and laughing fits. Gene imprinting disorders on chromosome 11p15 cause Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS). If maternal genes are inactivated, BWS occurs, and SRS occurs if paternal genes are inactivated. Temple syndrome (TS) and Kagami-Ogata syndrome (KOS) are caused by disruption of the gene imprinting of the 14q32 domain. TS is caused by the inactivation of the paternal genes, and KOS is caused by the inactivation of the maternal genes. BWS and KOS are associated with overgrowth and omphalocele, further, BWS is also associated with an increased risk of embryonal tumors. SRS and TS are associated with low birth weight, short stature, triangular face shape and clinodactyly, but there are differences between them. The aim is to describe mechanisms of UPD formation, the importance of gene imprinting and give an overview of the most relevant UPD syndromes. |
