# Novel compound heterozygous OBSCN variants in Chinese children with congenital pulmonary airway malformation

## TL;DR

This study identifies mutations in the OBSCN gene in Chinese children with congenital pulmonary airway malformation, suggesting a potential role in the condition's development.

## Contribution

The study reports novel compound heterozygous OBSCN variants in CPAM patients and explores the gene's role in lung development.

## Key findings

- Compound heterozygous OBSCN mutations were identified in two CPAM patients.
- OBSCN protein expression was reduced in CPAM lung tissue and during mouse lung development.
- OBSCN appears to play a key role in the pseudoglandular stage of lung development.

## Abstract

Congenital pulmonary airway malformation (CPAM) belongs to rare lung abnormalities which may result in poor lung development outcomes. However, the etiology of CPAM has not been well described.

In this study, whole-exome sequencing (WES) technology was used to sequence 9 CPAM families to screen the pathogenic genes and their mutations for CPAM. Sanger sequencing was performed for verify the functions of these mutations.

We found compound heterozygous mutations in OBSCN gene in two patients with CPAM: one with p.G8837A mutation inherited from her father and p.G1126S mutation inherited from her mother; the other with p.R5167W mutation inherited from his father and p.A7475T mutation inherited from his mother. Immunofluorescence results showed that the expression of OBSCN protein in the central lung tissue of CPAM patients was lower than that in the distal lung tissue of the lesion, and the expression of OBSCN protein was decreased in OBSCN mutated. We further explored the expression of OBSCN during mouse lung development, confirming that the gene mainly acts on the pseudoglandular stage.

The OBSCN gene may play a key role in pseudoglandular stage during mouse lung development. The mutation of OBSCN gene may play a role in promoting the occurrence of CPAM, providing a possible therapeutic target for clinical intervention of CPAM.