Objective: We are presenting two individuals with biallelic C-C chemokine receptor type 2 (CCR2) deficiency carrying the novel c.644C>T p.L215P variant, who presented with chronic respiratory symptoms during infancy and developed multiple diffuse cystic lesions during childhood. Methods: The patients were diagnosed by means of whole exome sequencing and functional validation of the variant was performed in primary patient cells. Results: While size and extent of the cysts were stable over years, progressive lung function decline was noted in adolescence and adulthood respectively. The CCR2 p.L215P variant was found to be loss-of-expression and patient monocytes displayed a migration defect upon stimulation with the CCR2 ligand C-C motif ligand 2 (CCL2). Conclusion: With a follow-up of up to 25 years, this report expands our understanding of lung disease in CCR2 deficiency and offers another monogenic cause of cystic lung disease. Early genetic diagnosis of affected individuals might allow potentially curative treatment by haematopoietic stem cell transplantation.
Multicystic Interstitial Lung Disease Due to a Novel Biallelic C-C Chemokine Receptor Type 2 Variant / Herkner, M.; Rapp, C.; Graeber, S. Y.; Marx, C.; Rambuscheck, C.; Reu-Hofer, S.; Emiralioglu, N.; Kiper, N.; Gilea, A. I.; Notaroberto, I.; Baruffini, E.; Temmesfeld-Wollbrück, B.; Klein, C.; Wen, H.; Stahl, M.; Griese, M.; Gothe, F.. - In: PEDIATRIC PULMONOLOGY. - ISSN 8755-6863. - 60:5(2025), pp. e71135.1-e71135.8. [10.1002/ppul.71135]
Multicystic Interstitial Lung Disease Due to a Novel Biallelic C-C Chemokine Receptor Type 2 Variant
Gilea A. I.;Notaroberto I.;Baruffini E.;
2025-01-01
Abstract
Objective: We are presenting two individuals with biallelic C-C chemokine receptor type 2 (CCR2) deficiency carrying the novel c.644C>T p.L215P variant, who presented with chronic respiratory symptoms during infancy and developed multiple diffuse cystic lesions during childhood. Methods: The patients were diagnosed by means of whole exome sequencing and functional validation of the variant was performed in primary patient cells. Results: While size and extent of the cysts were stable over years, progressive lung function decline was noted in adolescence and adulthood respectively. The CCR2 p.L215P variant was found to be loss-of-expression and patient monocytes displayed a migration defect upon stimulation with the CCR2 ligand C-C motif ligand 2 (CCL2). Conclusion: With a follow-up of up to 25 years, this report expands our understanding of lung disease in CCR2 deficiency and offers another monogenic cause of cystic lung disease. Early genetic diagnosis of affected individuals might allow potentially curative treatment by haematopoietic stem cell transplantation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
