Author/Editor		Trebušak-Podkrajšek, Katarina
Title		Genetska diagnostika bolnikov z avtoimunskim poliglandularnim sindromom
Type		monografija
Place		Ljubljana
Publisher		Univerza v Ljubljani, Medicinska fakulteta
Publication year		2006
Volume		str. 104
Language		slo
Abstract		Autoimmune polyglandular syndromes are defined associations of autoimmune endocrine diseases with accompanied autoimmune nonendocrine disorders. Currently there are four types of autoimmune polyglandular syndromes with different disease components, genetic features and frequency. Autoimmune polyglandular syndrome type 1 (APS-1) is a rare autosomal recessive disease associated with mutations in the AIRE gene. In contrast to APS-1, other types of APS (APS-2, APS-3 and APS-4) are genetically complex diseases. Individual diseases associated in those symptoms are also present in APS-1. Clinical and mutational characteristics of 21 APS-1 patients and 21 patients with APS-2, APS-3, APS-4, isolated autoimmune disorders and unclassified associations of autoimmune disorders from different populations were investigated. Three novel mutations were identified among 9 different AIRE gene mutations detected in 21 APS-1 patients. R257X mutation in exon 6 was the most frequent AIRE gene mutation detected in homozygous state in eleven patients. Slovenian APS-1 patients with R257X mutation had microsatellite markers nearby gene AIRE haplotypes typical for middle-European populations. The first novel mutation was an intronic mutation 653-7 -SdeICTC affecting proper splicing of intron 5 by using nearby new acceptor splice site as demonstrated by AIRE mRNA analysis. This is the first report of an intronic mutation investigated on the mRNA level in an APS-1 patient. Novel deletion 540de1G in exon 5 and novel duplication in exon 9 (1064-1068dupCCCGG) are frame shift mutations leading to premature truncation of the AIRE protein. The prevalence of APS-1 in Slovenian population was estimated to be 1 : 43 000, which is significantly higher as compared to the neighbouring populations. (Abstract truncated at 2000 characters)
Descriptors		POLYENDOCRINOPATHIES, AUTOIMMUNE POLYMORPHISM, RESTRICTION FRAGMENT LENGTH MICROSATELLITE REPEATS BASE SEQUENCE POLYMERASE CHAIN REACTION