Genetic screening of adenosine triphosphate-binding cassette transporter A3 gene variants in elderly patients with interstitial lung diseases
10.3760/cma.j.issn.0254-9026.2023.08.007
- VernacularTitle:老年人间质性肺疾病三磷酸腺苷结合盒转运子A3基因变异筛查
- Author:
Lyu LIU
1
;
Jishi LIU
;
Yue SHENG
;
Liangliang FAN
;
Hong PENG
;
Hong LUO
Author Information
1. 中南大学湘雅二医院呼吸与危重病医学科，长沙 410011
- Keywords:
Lung diseases, interstitial;
Pulmonary surfactant-associated proteins;
Gene mutations
- From:
Chinese Journal of Geriatrics
2023;42(8):927-931
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To screen mutations of the adenosine triphosphate(ATP)-binding cassette transporter A3(ABCA3)gene in elderly Chinese individuals with lung interstitial diseases(ILDs)and to analyze the clinical characteristics of ILDs in elderly patients.Methods:A prospective study, After further image analysis of patients diagnosed with interstitial lung diseases between September 2015 and December 2018 at the Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital of Central South University, 103 patients were willing to provide peripheral blood samples and signed informed consent.DNA samples were extracted and whole exome sequencing was performed to screen ABCA3 gene mutations.Clinical data of patients were summarized and analyzed.Results:Seven rare variants of the ABCA3 gene were identified in 6 patients, with a mean age of 67 years(69-73 years)and an equal sex distribution, and 33.3%(2/6)were smokers.The most notable presentation was diffuse lung lesions.Patients' final diagnoses included idiopathic pulmonary fibrosis(IPF, 3/6), nonspecific interstitial pneumonia(NSIP, 1/6), and IgG4-related lung disease(2/6). Meanwhile, compound heterozygous mutations of the ABCA3 gene responsible for IPF were identified in patient No.39, including p. Asp1465Asn, p.Leu3Vval and p. Val93Ile3, a new finding in patients with ILDs.Conclusions:ABCA3 mutation-related lung interstitial diseases exhibit variable characteristics, with differences in the age of onset, clinical manifestations, imaging features and prognosis between patients.ABCA3 mutations responsible for early-onset ILDs are mostly homozygous or compound heterozygous and usually highly pathogenic nonsense mutations.In contrast, ABCA3 mutations identified in elderly patients with ILDs are often missense mutations, a possible explanation for the variability of ILDs in the elderly.Since patients with ILDs caused by ABCA3 variants respond poorly to currently available treatment options, early genetic diagnosis may benefit patients by enhancing disease awareness.
