Aim: Very little is known about the relationship between genotype and phenotype of cystic fibrosis (CF) from the Turkish children. The aim of the study was to analyze the genotype and phenotype of 24 children with CF and to investigate the correlation between type of mutation in cystic fibrosis transmembrane conductance regulator (CFTR) protein gene and clinical manifestation of the disease.
Methods: Patients were evaluated retrospectively and prospectively. History, clinical findings, sweat test and mutation analysis were used for the definitive diagnosis of CF. Phenotypical features of 24 cases were evaluated according to clinical findings. We compared the clinical phenotype and age at diagnosis, genotypic features. A total of 36 mutations were analyzed by polymerase chain reaction (PCR) and reverse hybridization methods. Statistical analysis was done by using χ2, Fisher exact and Pearson correlation tests.
Results: The mean age of the cases that were admitted to our out-patient clinic was 5.3±4 years. The median age of diagnosis was three months. Parents were consanguineous in 37.5% of cases and loss of a sibling at one year of age was stated in a quarter. The most frequent symptom was recurrent diarrhoea (79.2%) and there was severe growth retardation in 12 (50%) and pseudo-Bartter (PB) syndrome in 11 of the cases. The incidence of PB was higher in cases that were diagnosed at one year of age. Out of 18 cases with mutation analysis, nine (50%) were positive for DF508 mutation, and four cases were homozygous out of nine cases. Two separate mutations were determined in two cases with severe clinical picture. The incidence of respiratory tract infection during the admission was lower in DF508 positive cases (P=0.016). There was no statistically significant relation between DF508 positivity and diarrhea, severe growth retardation and PB (P>0.05). The other mutations that were determined in our patients were rarely seen mutations such as 3120+1 G-A, R347P, 1677delTA, 2789+5G-A, 2183AA-G, and R1066C.
Conclusion: DF508 mutation rates in our cases diagnosed in early childhood were higher than the rates reported previously in Turkish children. The definition of molecular defect in CFTR gene has an impact on verifying the diagnosis and decreasing morbidity and mortality. An adequately large sample size is needed to evaluate the mutation profiles and genotype-phenotype characteristics in our country.