Ciliary and immune dysfunctions and their genetic background in patients with non-cystic fibrosis bronchiectasis in Central Iran.

OBJECTIVE: Bronchiectasis is usually caused by recurrent bacterial infections and is characterized by irreversible dilation of the bronchi. In this study, we aimed to give an overview of the genetic backgrounds of patients with non-cystic fibrosis bronchiectasis (NCFB) that have been suspected to an underlying ciliary dysfunction or inborn error of immunity (IEI).
METHOD: This is a retrospective cross-sectional study. Seventy-one NCFB patients who were referred to the Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran, from 1996 to 2020 were included. These patients were referred to this center for immunological and genetic evaluation. Genetic analysis with whole-exome sequencing and Sanger sequencing was confirmed in 30 patients. However, the genetic evaluations of 41 patients were either still under evaluation or the patients had refused to be genetically evaluated. RESULT: Thirty-eight of our 71 patients (53.52%) were diagnosed with ciliary dysfunction and the detected mutations included mutations in the CCDC65, DNAH11, RSPH1, CCDC40, and GAS8 genes as well as a novel mutation. Thirty-three patients (46.47%) had an IEI and the detected mutations included mutations of the following genes: TNFRSF13B, PTPN2, ZNF341 BTK, TCF3, CD79a, PIK3CD, JAGN1, WAS, RFXANK, STK4, GSDMD, and NEMO.
CONCLUSION: This study presents an overview of the underlying ciliary and immune dysfunctions and their genetic mutations in NCFB in a highly consanguine population. This would give us a better understanding of the etiologies and the known and novel genetic mutations in NCFB in Iran and, in turn, in the Middle East and North Africa (MENA) region.