engleski

Genotype-phenotype correlation in Croatian CF patients

Cystic fibrosis (CF) is one of the most common inherited diseases among whites with more than 1000 mutations in CFTR gene. The aim was to identify the most frequent CFTR mutations with genotype-phenotype correlation in CF patients in Croatia. PATIENTS AND METHODS: We have included 47 patients with CF from the Children’ s Hospital Zagreb, Croatia. Most of the patients were screened for 16 common mutations, while some of them were screened with INNO LiPa DNA probe assay for 29 CF mutations and Tn polymorphism. RESULTS: We have identified 79% of CF chromosomes with 7 different CFTR mutations: Δ F508 (66 %), G542X (3.2%), R117H (3.2%), N1303K (2.1%), 1717-1G-A (1.1%), R1162X (1.1%) and 621+1G>T (1.1%). All 17 Δ F508/ Δ F508 homozygotes had severe phenotype and pancreatic insufficiency (PI). Three G542X/∆ F508 compound heterozygotes, one 1717-1G-A/∆ F508, one R1162X/∆ F508 and two N1303K/∆ F508 patients revealed « classical» CF, while 621+1G>T/ ∆ F508 patient had PS (pancreatic sufficiency). One Δ F508/ R117H patient had serious clinical course, while another revealed mild phenotype. From 15 Δ F508/N patients, 6 had PS and all 3 N/N patients had chronic pulmonary disease, but PS. CONCLUSIONS: A total of 79% of CF chromosomes in Croatian CF patients consist of 7 different mutations (Δ F508, R117H, G542X, 1717-1G-A, N1303K, R1162X, 621+1G>T). The most frequent mutation is ∆ F508 with high frequencies of R117H and G542X. Severe clinical course and PI are present in 100% of Δ F508 homozygotes and in 80% of compound ∆ F508 heterozigotes while 40% of Δ F508/N and all of N/N patients had mild clinical course. There is a need for further analysis and gene sequencing in order to identify unknown mutations which could be the mild ones modifying the clinical course of classical CF into the atypical one.

genotype-phenotype correlation; cystic fibrosis; Croatia

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