BRIEF RESEARCH REPORT article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
Whole exome sequencing identified two novel mutations of ACD in Chinese patients with idiopathic pulmonary fibrosis
Liang-Liang Fan
Gao-Hui Cao
Hui Yang
Qian Wang
Hong Luo
Lv Liu
Central South University, Changsha, China
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Abstract
ABSTRACT Idiopathic Pulmonary Fibrosis (IPF) is a progressive, age-related, and distinct form of fibrosing interstitial pneumonia with an unknown etiology. Previous studies have indicated that mutations in the ACD Shelterin Complex Subunit and Telomerase Recruitment Factor (ACD) gene are associated with the development of IPF. This study aims to investigate ACD mutations in Chinese patients with interstitial lung diseases (ILDs). A total of 124 ILD patients were enrolled in this study. Whole exome sequencing and Sanger sequencing were performed to identify genetic variants in these individuals. Mutant plasmids were constructed and transfected into the A549 cell line to conduct in vitro functional assays. Among the 124 patients, two novel ACD mutations (c.884G>A/p.S295N and c.1074C>G/p.H358Q) were identified in two Chinese families with a history of IPF. Functional analyses revealed that both mutations compromise the stability of the TPP1 protein, leading to reduced TPP1 expression. This downregulation subsequently decreases DKC1 expression, ultimately resulting in telomere shortening and contributing to IPF pathogenesis. To the best of our knowledge, this study represents the first report of ACD mutations in an Asian population with IPF. Our findings broaden the mutation and population spectrum of ACD deficiency.
Summary
Keywords
ACD mutation, Idiopathic Pulmonary Fibrosis, shelterin complex, Telomere, TPP1
Received
11 December 2025
Accepted
17 February 2026
Copyright
© 2026 Fan, Cao, Yang, Wang, Luo and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Liang-Liang Fan
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