A Novel Potentially Pathogenic DNAH5 Variant in a Patient with Kartagener’s Syndrome from Ardabil Province: A Case Report

Kartagener's syndrome is a rare autosomal recessive genetic disorder characterized by a clinical triad: chronic sinusitis, bronchiectasis, and situs inversus. This triad includes persistent inflammation of the sinuses, abnormal dilation of the bronchi, and a mirror-image arrangement of internal organs. The syndrome is commonly associated with mutations in genes critical for ciliary function, particularly DNAH5, which encodes a protein essential for normal ciliary motility. This case report describes a novel pathogenic variant in the DNAH5 gene identified in a 2-year-old Iranian female diagnosed with Kartagener's syndrome. She presented with recurrent episodes of pneumonia beginning in the neonatal period, with symptoms first appearing at 12 days of age. Notably, she was born to consanguineous parents, although no family history of recurrent pneumonia or infertility was reported. The diagnosis was supported by the presence of dextrocardia, consistent with her situs inversus. Among the approximately 49 genes implicated in primary ciliary dyskinesia (PCD) and Kartagener's syndrome, mutations in DNAH5 are a known cause of chronic respiratory infections and organ laterality defects. In accordance with the American College of Medical Genetics and Genomics (ACMG) guidelines, the variant DNAH5 (NM_001369.3): c.1190_1193del (p.Phe397Ter) was classified as likely pathogenic based on criteria PS1 and PM2. Its very low allele frequency in genomic databases, including Iranome, along with its consistency with ACMG criteria and the patient’s clinical manifestations, supports the classification of this variant as pathogenic.