PRJNA739066
mutations of DNAH5 identified in a pediatric patient with Kartagener syndrome
Kartagener syndrome is a subtype of primary ciliary dyskinesia that may exhibit various symptoms including neonatal respiratory distress and frequent infections of the lung, sinus and middle ear because of the impaired function of motile cilia. In addition to typical symptoms of primary ciliary dyskinesia, patients with Kartagener syndrome also show situs inversus. It is an autosomal recessive disorder which is mostly caused by mutations in DNAH5. Kartagener syndrome is often underdiagnosed due to challenges in the diagnosis process. As next-generation sequencing becomes widely used in clinical laboratories, genetic testing provides an accurate approach to the diagnosis of Kartagener syndrome.Case presentation: A 7-year-old female patient presented with runny nose of six years duration and recurrent cough with phlegm of two years duration. Kartagener syndrome was diagnosed through diagnostic tests such as nasal nitric oxide (NO) concentration and transmission electron microscopy, and after performing other exams that corroborated the diagnosis, such as computed tomography, bronchoscopy and hearing test. Whole-exome sequencing was performed for the patient and both parents. The pediatric patient was diagnosed as Kartagener syndrome with the typical symptoms of ciliary dyskinesia including bronchiectasis, sinusitis, conductive hearing loss and situs inversus along with a reduced nasal NO concentration and ciliary abnormalities. The patient carried two novel compound heterozygous mutations in DNAH5, NM_001369:c.12813G>A (p. Trp4271Term) and NM_001369:c.9365delT (p. Leu3122Term). Both mutations lead to premature stop codons and thus are pathogenic. The p. Trp4271Term and p. Leu3122Term mutations were inherited from the father and the mother of the patient individually. A literature review was also conducted to summarize DNAH5 mutations in pediatric patients with Kartagener syndrome across different ethnic groups.