Author/Editor		Trebušak, Katarina
Title		Preiskave gena AIRE pri bolnikih z avtoimunskim poliglandularnim sindromom tip 1 (APS-1)
Type		monografija
Place		Ljubljana
Publisher		Medicinska fakulteta
Publication year		2001
Volume		str. 49
Language		slo
Abstract		Autoimmune polyglandular syndrome type 1 (APS-1) is a rare autosomal recessive disease. It is characterized by presence of two out of three major clinical symptoms: hypoparathyroidism, Addison's disease and mucocutaneous candidiasis. Several other enocrine or nonendocrine disorders may be present. The aethiology of APS-1 is associated with mutations in the AIRE (autoimmune regulator) gene encoding a protein that contains motifs suggesting a role as a transcriptional regulator. Mutational analyses of the AIRE gene was performed in nine APS patients from eight families, their parents and healthy siblings using direct sequencing and restriction fragment length polymorphism. The aim of this study was to establish the genetic diagnosis of the APS-1 patients, to determine whether healthy brothers and sisters of the patients will develop APS-1 and to determine phenotype-genotype correlation in APS-1 patients. Six out of nine analysed patients were homozygous for the mutation R257X that is most frequent in the Finnish population. Their parents and four analysed siblings of two patients were heterozygous for R257X. Since siblings were heterozygous, they will most probably not develop APS-1. One patient was found to be compound heterozygous for the R257X and a duplication of 23 bp in exon 1 (30-52dup23bp). This duplication is a novel mutation and changes the reading frame causing premature truncation at the beginning of the coding region. Two out of nine analysed patients did not have a mutation in the coding region and the inton/exon boundaries. Therefore their diagnosis was not confirmed. Mutations may exist in promotor region or in intron regions that were not analysed. (Abstract truncated at 2000 characters).
Descriptors		POLYENDOCRINOPATHIES, AUTOIMMUNE GENES, REGULATOR MUTATION POLYMORPHISM, RESTRICTION FRAGMENT LENGTH PHENOTYPE GENOTYPE HAPLOTYPES POLYMERASE CHAIN REACTION BASE SEQUENCE EXONS