Reporting three rare pathogenic variants at the CFTR gene in two unrelated Iranian Azeri children with cystic fibrosis

Abstract Background Cystic fibrosis (CF) is an autosomal recessive inherited life-threatening disease that causes changes in the electrolyte transport system, leading to high absorption of sodium and water. Disease-causing variants of the CFTR gene are responsible for this disease. In the present study, three rare pathogenic variants were identified in two unrelated Iranian Azeri children with CF. Case presentation One child affected with CF was found to have two rare variants, c.1545_1546delTA and c.3196C > T, detected through Sanger sequencing of the entire coding region and promoter of the CFTR gene. Another patient was identified as compound heterozygous for the variant c.1545_1546delTA and a rare variant, c.2998delA, which has not been previously reported. The variants were found to be in trans, as both parents were heterozygous for the variants. Conclusion The rare variant c.1545_1546delTA has been previously reported as a known variant in certain populations, including Azeris in northwest Iran. Our results, along with previous findings, suggest that this variant may be considered a founder mutation in specific geographical regions. The variant c.2998delA has not been previously reported as pathogenic. Following the guidelines of the American College of Genetics and Genomics and considering the proband's symptoms, we classified this variant as pathogenic based on criteria PVS1, PS4, PM3, PP1, and PM2. The identified variants in the CFTR gene as well as the previously reported variants could serve as a basis for future genetic counseling and prenatal diagnosis in Iran.