Journal article
Biallelic LAMP3 Variants in Five Families with Interstitial Lung Disease: Evidence of a Disease-Gene Association
Genetics in medicine, Vol.28(4), 102531
04/2026
DOI: 10.1016/j.gim.2026.102531
PMID: 41653023
Abstract
Genetic causes of surfactant dysfunction are associated with childhood interstitial lung disease (chILD). Lysosome-associated membrane glycoprotein 3 (LAMP3) is highly expressed within lamellar bodies of alveolar epithelial type II cells, and variants in LAMP3 have recently been suggested as a novel cause of chILD. This study describes the phenotypes of participants with biallelic variants in LAMP3 and presents functional studies evaluating the role of specific LAMP3 variants.
Phenotypic data was collected through chart review and clinical evaluation. In vitro effects of LAMP3 variants were evaluated through immunohistochemistry, WB, and flow cytometry.
Thirteen participants were identified with biallelic variants in LAMP3. They presented with variable phenotypes ranging from neonatal respiratory distress to asymptomatic in adulthood. All symptomatic participants demonstrated ground glass opacities early in life and lung fibrosis later in life. For one participant, BAL analysis showed abnormal surfactant protein composition and lung biopsy revealed irregular LB. In vitro studies in lung epithelial cells with induced expression of specific LAMP3 variants demonstrated reduced protein expression and abnormal glycosylation.
Biallelic LAMP3 variants are associated with an interstitial lung disease phenotype with variable expressivity. Evaluation for LAMP3 variants should be considered in individuals with unexplained interstitial lung disease.
Details
- Title: Subtitle
- Biallelic LAMP3 Variants in Five Families with Interstitial Lung Disease: Evidence of a Disease-Gene Association
- Creators
- Laura A Keehan - Stanford UniversityHitomi Ono-MinagiMohamad Hadhud - Hebrew University of JerusalemJonathan Rips - Hadassah Medical CenterDaniel M Hinds - University of IowaAnthony J Fischer - University of IowaJennifer A Bartlett - University of IowaPaul B. McCray Jr - University of Iowa, Pulmonary MedicineNada Qawasmi - Al-Quds UniversityNadia Nathan - InsermCamille Louvrier - Sorbonne UniversitéTifenn Desroziers - Sorbonne UniversitéMarkus Damme - Christian-Albrechts-Universität zu KielMatthias Griese - Ludwig-Maximilians-Universität MünchenDaniel J Wegner - St. Louis Children's HospitalF Sessions Cole - Mallinckrodt (United States)Jennifer A Wambach - St. Louis Children's HospitalMatthew T Wheeler - Stanford MedicinePeter D Burbelo - National Institutes of HealthDevon E Bonner - Stanford MedicineJonathan A Bernstein - Stanford MedicineJohn A Chiorini - National Institute of Dental and Craniofacial ResearchOded Breuer - Hadassah Medical CenterCarlos Milla - Stanford UniversityUndiagnosed Diseases Network
- Resource Type
- Journal article
- Publication Details
- Genetics in medicine, Vol.28(4), 102531
- DOI
- 10.1016/j.gim.2026.102531
- PMID
- 41653023
- NLM abbreviation
- Genet Med
- ISSN
- 1098-3600
- eISSN
- 1530-0366
- Publisher
- Elsevier
- Grant note
- Roy J. Carver Chair in Pulmonary ResearchNHLBI: R03 TR00481 NIH NINDS: U01NS134358 NIH NIDCR: Z01-DE00695 NIH NHLBI: R01HL149853 Children's Discovery Institute at St Louis Children's Hospital/Washington University School of MedicineRoss Mosier Research Laboratories Gift FundGerman Research Foundation (Deutsche Forschungsgemeinschaft): 970/9-2 German Center for Lung Research (Deutsches Zentrum fur Lungenforschung)
Research reported in this manuscript was supported in part by the NIH NINDS U01NS134358, NIDCR Z01-DE00695, and NHLBI R01HL149853. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research was also supported by the Children's Discovery Institute at St Louis Children's Hospital/Washington University School of Medicine. The work of C. Milla was supported by the Ross Mosier Research Laboratories Gift Fund. The work of M. Griese was supported by German Research Foundation (Deutsche Forschungsgemeinschaft) 970/9-2 and the German Center for Lung Research (Deutsches Zentrum fur Lungenforschung) . The work of P. McCray was supported by the Roy J. Carver Chair in Pulmonary Research and NHLBI R03 TR00481.
- Language
- English
- Electronic publication date
- 02/03/2026
- Date published
- 04/2026
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9985139313102771
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