Analiza uwarunkowań genetycznych wrodzonej naczyniakowatości krwotocznej choroby Rendu-Oslera-Webera – doniesienia wstępne

Introduction Hereditary haemorrhagic telangiectasia (HHT) known also as Rendu-Osler-Weber syndrome is an autosomal dominant disorder characterized by localized angiodysplasia due to mutations in ENG (endoglin, 9q34.1) or ALK-1 gene (the activin receptor-like kinase 1, 12q13). ENG and ALK-1 are found associated with two disease subtypes designated as HHT1 and HHT2, respectively. Subtype HHT1 remains in the frame of interest of laryngology because of frequent bleeding in head and neck region. Material and method The study was designed to identify a genetic background in a large family (29 individuals) with diagnosed HHT. Pedigree analysis showed autosomal dominant pattern of inheritance. Study design comprised segregation analysis to determine locus with subsequent direct sequencing of the gene. Four microsatelite markers (d9s61, d9s65, d12s368, d12s347) with high frequency of heterozygosity in population study were used. Results The results concerning heterozygosity ranged from 15% to 53%. The established differences were not sufficient enough to indicate co-segregation of the studied loci. DNA sequence analysis in exon 11 of ENG gene did not reveal mutations. The latter result could be explained by an occurrence of mutations in other exons of ENG. Conclusions The study requires continuation for gene identification and precise genotype-phenotype correlation aiming for an improvement of HHT1 therapy.