engleski

Genotype-phenotype correlation in Croatian cystic fibrosis patients

BACKGROUND:Cystic fibrosis (CF) is the most common recessive disorder caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator Gene (CFTR). The distribution of over 800 different CFTR mutations depends on the ethnic and geographic origin. OBJECTIVE: To determine genotype-phenotype correlation in Croatian CF patients in order to establish weather patients with different genotypes showed differences of pheotypic expression in pancreatic and pulmonary disease. METHODS: The clinical diagnosis of CF was made according to the high sweat chloride values, chronic pulmonary disease, pancreatic insufficiency and Pseudomonas colonisation. The molecular analyisis of the 16 most common CFTR mutations (according to the data from Cystic Fibrosis Genetic Analysis Consortium) was performed. RESULTS: The analysis of 98 chromosomes revealed the frequency of deltaF508 in 59% of Croatian patients. R117H was present in 4%, G542X in 3%, 1717-1G-A in 3%, N1303 in 2%, and G85E and R1162X in 1%. Further analysis of remaining CF alleles is planned. All deltaF508 homozygous patients had a severe phenotype ; an early age at diagnosis, high sweat chloride values, pancreatic insufficiency, similar severity of lung disease. Severity of the clinical course in deltaF508 heterozygous patients depended on another mutation present in CFTR gene ; heterozygotes with N1303K, G542X, 17171G-A, R1162X and G85E had severe CF phetoype with pancreas insufficiency, but variable pulmonary disease. The heterozygous patients with R117H mutation revealed mild or severe clinical course with variable pancreatic phenotype but consistent mild pulmonary disease.

cystic fibrosis; mutations; pheotype

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