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

BACKGROUND: LAMP3 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. METHODS: LAMP3 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. FINDINGS: Two heterozygous LAMP3 variants (Y302Qfs

• Louvrier, C.
• Desroziers, T.
• Soreze, Y.
• Delgado Rodriguez, M.
• Thomas, L.
• Nau, V.
• Dastot-Le Moal, F.
• Bernstein, J. A.
• Cole, F. S.
• Damme, M.
• Fischer, A.
• Griese, M.
• Hinds, D.
• Keehan, L.
• Milla, C.
• Mohammad, H.
• Rips, J.
• Wambach, J. A.
• Wegner, D. J.
• Amselem, S.
• Legendre, M.
• Giurgea, I.
• Karabina, S. A.
• Breuer, O.
• Coulomb l'Herminé, A.
• Nathan, N.