Analysis Variants of the CFTR Gene in Iranian Cystic Fibrosis Patients

Abstract

Background: Cystic fibrosis (CF) is known as one of the most common autosomal recessive disorders, which is caused by mucosal glands. A deficiency in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which encodes a chloride channel, triggers damage to epithelial cells in respiratory ducts, pancreas, intestine, genital ducts in males, liver system, and sweat glands Objectives: The aim of this study was to complete sequencing of the 27 exons of the CFTR gene to screen the spectrum of the variants in patients from all over Iran from different ethnicities. Methods: This is a descriptive-analytical study that was performed during eleven years from 2010 to 2021. 345 patients were referred to Tehran Medical Genetics Laboratory by specialists. These patients were categorized into four groups. The first group included clinically confirmed patients of CF, having clinical features and biochemical abnormalities, plus positive sweat chloride test. The second group included couples with an alive or deceased child affected. The third group included CBAVD (congenital bilateral absence of the vas deferens) cases, and the fourth group included prenatal diagnosis who looking for carrier detection or her spouse is affected with CBAVD. Results: Fifty-four variants and five deletions were found from 345 patients, the most common frequent variant were c.1521_1523delCTT ([delta]F508) (47 (6.81%)), c.1000C>T (R334W, 31 (4.45%)), c.1911delG (2043delG, 25 (3.62%)), c.2051_2052delAAinsG (2183AA->G, 15 (2.17%)), c.1624G>T (G542X, 12 (1.74%)), c.1697C>A (A566D, 12 (1.74%)), c.1210-12T [5] (9(1.30%)) and c.3196C>T (R1066C,7 (1.01%)) respectively and frequency of other variants were less than 1%. Deletion in some exons was established by MLPA assay, the most common deletion was c. (53+1_54-1) _ (164+1_165-1) del (CFTRdele2, 7 (1.01%)). Conclusions: In conclusion, the present study improves the knowledge of CF in Iran with respect to carrier analysis, and genetic counselling. Also, it helps to develop a cost-effective newborn screening program.