Novel compound heterozygous mutations of DNAH5 identified in a pediatric patient with Kartagener syndrome: case report and literature review

Abstract

Background 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 6 years duration and recurrent cough with phlegm of 2 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. Conclusions Our study provides a good example of the diagnosis of Kartagener syndrome in pediatric patients using a series of diagnostic tests combined with genetic testing. Two novel loss-of-function mutations in DNAH5 were identified and validated in a pediatric patient with Kartagener syndrome.

A novel homozygous RSPH4A variant in a family with primary ciliary dyskinesia and literature review

“…Our literature review revealed that the hearing loss was different depending on the gene involved ( Table 1 ). Variants in CCDC114 cause sensorineural hearing loss (SNHL) ( Li et al, 2019 ), while variants in CCN O, CDH3 , DNAH5 and OFD1 cause conductive hearing loss (CHL) ( Bukowy-Bieryllo et al, 2019 ; Fan et al, 2019 ; Henriques et al, 2021 ; Wang et al, 2021 ; Yang et al, 2022 ). In addition, the clinical findings were summarized to conclude the different symptoms, age at onset or diagnosis among PCD patients with CHL and SNHL ( Table 2 ).…”

Novel homozygous mutations of DNAH5 in Kartagener syndrome

“…Genetic testing is becoming more common and feasible in the diagnosis of KS due to recent advances in next-generation sequencing. DNAH5 is reportedly the most frequently mutated gene in patients with PCD [ 3 , 4 ]. It encodes the dynein axonemal heavy chain 5 protein, which is a component of the outer dynein arm (ODA).…”

Next-Generation Sequencing-Based Copy Number Variation Analysis in Chinese Patients with Primary Ciliary Dyskinesia Revealed Novel DNAH5 Copy Number Variations

“…At least 100 different pathogenic variants in the DNAH5 gene have been reported (Zariwala et al 1993 ; Hornef et al 2006 ; Emiralioğlu et al 2020 ; Wang et al 2021 ). However, the clinical significance of copy number variations (CNVs) in DNAH5 has rarely been reported.…”