# DNAH9 variants in children with post-infectious bronchiolitis/bronchitis obliterans

## TL;DR

This study explores how DNAH9 gene variants may be linked to a rare lung disease in children following severe infections.

## Contribution

The study identifies twelve DNAH9 variants in children with post-infectious bronchiolitis/bronchitis obliterans.

## Key findings

- Six pediatric patients with DNAH9 variants were found to have PIBO after severe infections.
- DNAH9 mutations included nonsense, splice site, and missense variants, all with low allele frequencies.
- The variants were predicted to be harmful or of uncertain significance, suggesting a possible role in PIBO.

## Abstract

Post-infectious bronchiolitis/bronchitis obliterans (PIBO) is a chronic irreversible obstructive lung disease that results in obstruction and/or obliteration of small airways. Previous reports have indicated that PCD-related gene mutations contribute to PIBO incidence. However, the relationship between DNAH9 variants and PIBO remains unclear. This study aimed to evaluate the association between DNAH9 mutations and the incidence of PIBO. In our cohort, 126 PIBO patients conducted Whole Exome Sequence (WES) test and twelve variants of DNAH9 gene were identified. Detailed clinical information, high-resolution computerized tomography and/or electronic bronchoscopy findings of the six pediatric children carried DNAH9 variants were systematically collected, meticulously reviewed, and rigorously analyzed. Clinical evaluation revealed three patients with bronchiolitis obliterans, two patients with bronchitis obliterans and one with both conditions. All patients had at least one previous bout of pneumonia, which in three cases was linked to Mycoplasma pneumoniae, in two cases to adenovirus infection, and in one case to co-infection with both pathogens. Genetic analysis of all cases identified six compound heterozygous DNAH9 mutations encompassing twelve variants: c.12,925 C > T (p.Arg4309*), c.5152-10G > T (-), c.4604 A > G (p.Gln1535Arg), c.12844-14T > C (-), c.4816T > C (p.Phe1606Leu), c.8831G > A (p.Arg2944Gln), c.9479 C > T (p.Ala3160Val), c.7415G > A (p.Arg2472Gln), c.5692G > T (p.Glu1898*), c.11,572 C > T (p.Arg3858Trp), c.11,176 C > T (p.Arg3726Trp), c.1010 C > T (p.Pro337Leu). These variants included two nonsense mutations, two mutations near splice sites, and eight missense mutations. All variants exhibited negligible or low minor allele frequencies based on the gnomAD database and were predicted to be variants of uncertain significance (VUS) or deleterious based on comprehensive bioinformatics analysis. Our findings suggest that DNAH9 compound complex variants may contribute to development of PIBO following severe M. pneumoniae and/or adenoviral infectious pneumonia in pediatric patients.