| Title: |
Surfactant Protein A2 Mutation in Early Onset Familial Pulmonary Fibrosis With Novel Skin Phenotype |
| Authors: |
Chroneos, Z.C.; Bascom, R.; Amatya, S.; Schneper, L.; Nelson, A.; Dimmock, A.E.F.; Umstead, T.M.; Liu, D.; Sheldon, K.; Broach, J.R. |
| Source: |
American Journal of Respiratory and Critical Care Medicine ; volume 211, issue Supplement_1, page A7644-A7644 ; ISSN 1073-449X 1535-4970 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2025 |
| Description: |
Introduction/Rationale: Familial pulmonary fibrosis (FPF) represents a subset of idiopathic pulmonary fibrosis cases, but the genetic basis for only a fraction of FPF patients has been determined. We report genetic analyses and phenotypes of a multigenerational cohort with early onset FPF. We further describe an unanticipated skin abnormality not previously reported and strictly linked to affected individuals. Methods: Clinical diagnosis and phenotyping included longitudinal chest computerized tomography, serial pulmonary function testing, thoracic lung biopsies, bronchoalveolar lavage and skin biopsies. Microarray analysis and genome sequencing were used to generate polymorphic profiles of the cohort. Skin punch biopsies were obtained from visually normal skin 4-6 cm below the midclavicular line and processed for histology, immunohistochemistry and isolation of fibroblasts for cell culture. Results: Affected family members displayed atypical parenchymal features as early as age 21, including ground-glass opacities, nodules and early cystic changes suggesting surfactant dysfunction. Progressive fibrosis and respiratory failure led to lung transplantation at age 32, 39 and 46 for three family members with a fourth referred for transplant evaluation at age 32. A fifth family member had mild interstitial changes detected at age 57 concurrent with a diagnosis of lung cancer. Additionally, several family members from previous generations died of FPF. Genetic analysis identified genomic regions on chromosomes 7, 10 and 17 that segregate only to affected family members as well as a rare variant in the SFTPA2 gene present in the affected members but also in several unaffected members. Variants in SFTPA2 have been previously linked to FPF. The variant causes a V187M substitution in the globular domain of the encoded Surfactant Protein A2 (SP-A2). Family members with early onset FPF showed an unusual separation of the skin epidermis, abnormal deposition of elastin as evidenced by pentachrome staining, poor growth ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1164/ajrccm.2025.211.abstracts.a7644 |
| Availability: |
https://doi.org/10.1164/ajrccm.2025.211.abstracts.a7644; https://academic.oup.com/ajrccm/article-pdf/211/Supplement_1/A7644/67057896/ajrccm_211_abstracts_a7644.pdf |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.8C07509D |
| Database: |
BASE |