Evidence map›Paper›PMID 40023045›Full record

ArticleEBioMedicine2025

Bi-allelic LAMP3 variants in childhood interstitial lung disease: a surfactant-related disease.

Camille Louvrier, Tifenn Desroziers, Yohan Soreze, Martha Delgado Rodriguez, Lucie Thomas, Valérie Nau, Florence Dastot-Le Moal, Jonathan A Bernstein, F Sessions Cole, Markus Damme and 16 more

Abstract readCase Reports
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In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
  2. Review
  3. Biallelic LAMP3 variants in 5 families with interstitial lung disease: Evidence of a disease-gene association.Genetics in medicine : official journal of the American College of Medical Genetics · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Dominant Form ofAmerican journal of respiratory and critical care medicine · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors.

Camille LouvrierSorbonne University, Inserm UMR_S933 Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital, Paris, France; Assistance Publique Hôpitaux de Paris, Medical Genetics Department, Armand Trousseau Hospital, Paris, France. Electronic address: camille.louvrier@aphp.fr.
Tifenn DesroziersSorbonne University, Inserm UMR_S933 Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital, Paris, France.
Yohan SorezeSorbonne University, Inserm UMR_S933 Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital, Paris, France; Assistance Publique Hôpitaux de Paris, Intensive Care Unit, Armand Trousseau Hospital, Paris, France.
Martha Delgado RodriguezSorbonne University, Inserm UMR_S933 Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital, Paris, France.
Lucie ThomasSorbonne University, Inserm UMR_S933 Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital, Paris, France.
Valérie NauAssistance Publique Hôpitaux de Paris, Medical Genetics Department, Armand Trousseau Hospital, Paris, France.
Florence Dastot-Le MoalAssistance Publique Hôpitaux de Paris, Medical Genetics Department, Armand Trousseau Hospital, Paris, France.
Jonathan A BernsteinDepartment of Pediatrics, School of Medicine, Stanford University, Stanford, CA, USA.
F Sessions ColeEdward Mallinckrodt Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
Markus DammeChristian-Albrechts-University Kiel, Biochemical Institute, Kiel, Germany.
Anthony FischerDepartment of Pediatrics, University of Iowa, Iowa City, IA, USA.
Matthias GrieseDepartment of Pediatric Pneumology, Dr von Hauner Children's Hospital, Ludwig-Maximilians-University, German Center for Lung Research, Munich, Germany.
Daniel HindsDepartment of Pediatrics, University of Iowa, Iowa City, IA, USA.
Laura KeehanDepartment of Pediatrics, School of Medicine, Stanford University, Stanford, CA, USA.
Carlos MillaDepartment of Pediatrics, School of Medicine, Stanford University, Stanford, CA, USA.
Hadhud MohammadHadassah Hebrew University Medical Center, Jerusalem, Israel.
Jonathan RipsHadassah Hebrew University Medical Center, Jerusalem, Israel.
Jennifer A WambachEdward Mallinckrodt Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
Daniel J WegnerEdward Mallinckrodt Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
Serge AmselemSorbonne University, Inserm UMR_S933 Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital, Paris, France; Assistance Publique Hôpitaux de Paris, Medical Genetics Department, Armand Trousseau Hospital, Paris, France.
Marie LegendreSorbonne University, Inserm UMR_S933 Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital, Paris, France; Assistance Publique Hôpitaux de Paris, Medical Genetics Department, Armand Trousseau Hospital, Paris, France.
Irina GiurgeaSorbonne University, Inserm UMR_S933 Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital, Paris, France; Assistance Publique Hôpitaux de Paris, Medical Genetics Department, Armand Trousseau Hospital, Paris, France.
Sonia Athina KarabinaSorbonne University, Inserm UMR_S933 Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital, Paris, France.
Oded BreuerHadassah Hebrew University Medical Center, Jerusalem, Israel.
Aurore Coulomb l'HerminéAssistance Publique Hôpitaux de Paris, Pathology Department, Sorbonne University, Armand Trousseau Hospital, Paris, France.
Nadia NathanSorbonne University, Inserm UMR_S933 Laboratory of Childhood Genetic Diseases, Armand Trousseau Hospital, Paris, France; Assistance Publique Hôpitaux de Paris, Pediatric Pulmonology Department, Reference Centre for Rare Lung Diseases (RespiRare), Armand Trousseau Hospital, Paris, France.

Funding

Functional Characterization of ABCA3 Genomic VariantsR01HL149853 · NHLBI · WASHINGTON UNIVERSITY · PI Jennifer Wambach · 2020 to 2026
$3.9M
NHLBI NIH HHS R01 HL149853
6 · The paper itself

Abstract

backgroundLAMP3 encodes a lysosomal membrane protein associated with lamellar bodies and has recently been proposed as a candidate gene for childhood interstitial lung diseases (chILD). Here, we identified two LAMP3 variants in a proband with chILD and performed functional validation of these variants as well as the previously reported variants to demonstrate the role of LAMP3 in pathology.

methodsLAMP3 variants were identified by exome sequencing. Ex vivo studies included mRNA analysis from nasal brushing and lung tissue and immunohistochemistry from lung biopsy. In vitro functional analyses in the A549 cell line included immunofluorescence staining and expression analysis of LAMP3. Interactions between LAMP3 and the surfactant protein (SP)-B and SP-C were evaluated by co-immunoprecipitation.

findingsTwo heterozygous LAMP3 variants (Y302Qfs∗2 and T268M) were identified in a 15 year old boy with chILD. LAMP3 mRNA revealed that the frameshift variant resulted in nonsense-mediated mRNA decay. Reduced LAMP3 expression was confirmed in the patient's lung tissue. Functional studies of the T268M and the previously reported G288R variant revealed reduced levels of the mutant proteins. In addition, impaired N-glycosylation and protein instability were demonstrated with the T268M variant. Finally, we provided evidence for an interaction between LAMP3 and SP-B and SP-C, revealing a direct link between LAMP3 and surfactant metabolism.

interpretationLAMP3 bi-allelic variants leading to LAMP3 dysfunction emerges as a cause of chILD associated with a heterogeneous phenotype that remains to be further defined. The close links between LAMP3 and surfactant metabolism could explain the pathophysiology of this genetic disease.

fundingNo specific funding.

Indexed as

AllelesLung Diseases, InterstitialLysosomal Membrane ProteinsMutationAdolescentExome SequencingGenetic Predisposition to DiseaseHumansLysosomal-Associated Membrane Protein 3MaleNeoplasm ProteinsPulmonary Surfactant-Associated Protein BPulmonary Surfactant-Associated Protein CLAMP3 protein, humanLysosomal-Associated Membrane Protein 3Lysosomal Membrane ProteinsNeoplasm ProteinsPulmonary Surfactant-Associated Protein BPulmonary Surfactant-Associated Protein CChildhood interstitial lung diseasesLAMP3Lung fibrosisSurfactant

Identifiers

PMID40023045
PMCPMC11914748

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.