Genetic investigation of sinopulmonary diseases in Vietnam: seeking specific causes from non-specific symptoms

TL;DR

This study explores the genetic causes of chronic lung and sinus diseases in Vietnam, identifying rare genetic variants linked to conditions like cystic fibrosis and primary ciliary dyskinesia.

Contribution

The study is the first to identify specific genetic variants for CF, PCD, and a potential DPB link in Vietnamese patients with non-specific respiratory symptoms.

Findings

Pathogenic variants in CFTR, DNAAF11, and RSPH1 were identified in patients with sinopulmonary diseases.

An intron2 variant of MUC22 was more common in patients with extensive bronchiolar lesions and bronchiectasis.

Genetic differences in Vietnamese patients highlight the need to consider ethnic variations in disease management.

Abstract

Sinopulmonary diseases are characterized by bronchiectasis (BE) and chronic rhinosinusitis, partly arising from clear genetic abnormalities such as cystic fibrosis (CF) and primary ciliary dyskinesia (PCD). However, the spectrum varies across ethnicities, and specifically, while considered rare in Southeast Asia, the current status in this region remains largely unknown. In this study, we investigated the clinical and genetic characteristics of patients with chronic symptoms affecting both the upper and lower airways in the northern region of Vietnam.

We recruited 200 patients with chronic rhinosinusitis and productive cough in Vietnam. Clinical characteristics including pulmonary function measurements and high-resolution chest computed tomography findings were collected. The patients’ median age was 49.0 years, with a median productive cough duration of 3 years. BE was identified in 43.8% of cases, most commonly affecting the right and left middle lung lobes (74.7% and 70.1%, respectively), and was associated with older age and bronchiolar lesions (BL). Extensive BL/BE representing 15.5% of cases (31/200), was associated with impaired pulmonary function, and seven exhibited respiratory symptoms before the age of 20. To elucidate the genetic basis of sinopulmonary diseases in patients with early onset or situs inversus, we performed genetic analyses, including targeted resequencing of genes for CF and PCD, as well as other candidate genes. Pathogenic variants identified in the CFTR gene were p.Trp401Ter and p.Asp979Ala only in one patient. NM_012472.6(DNAAF11):c.1A>G; p.Met1?, NM_080860.4(RSPH1):c.365+1G>A, and NM_080860.4(RSPH1):c.407_410del; p.Lys136MetfsTer6, all causative of PCD, were identified in the homozygous or hemizygous state in three different patients, respectively. WFDC2 genetic abnormalities were not identified. An intron2 variant of MUC22 (PBMUCL1), a candidate susceptibility gene for diffuse panbronchiolitis (DPB), was more frequently observed in patients with extensive BL/BE.

This is the first report in Vietnamese patients with non-specific upper and lower airway symptoms to identify genetic variants specific to CF and PCD, as well as another variant potentially associated with DPB. For the future management of sinopulmonary diseases or BE with unknown causes, ethnic differences based on their genetic etiology should be carefully considered.

The online version contains supplementary material available at 10.1186/s13023-025-04031-5.

Figures