# Multicystic Interstitial Lung Disease Due to a Novel Biallelic C‐C Chemokine Receptor Type 2 Variant

## TL;DR

This paper reports two individuals with a new CCR2 gene variant causing lung disease with cystic lesions and impaired cell migration, highlighting a potential genetic cause and treatment option.

## Contribution

Identifies a novel biallelic CCR2 variant as a monogenic cause of multicystic interstitial lung disease.

## Key findings

- Patients with CCR2 p.L215P variant showed chronic respiratory symptoms and cystic lung lesions.
- The CCR2 variant caused loss-of-expression and monocyte migration defects in response to CCL2.
- Long-term follow-up showed stable cysts but progressive lung function decline and potential for curative treatment via stem cell transplantation.

## Abstract

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.

The patients were diagnosed by means of whole exome sequencing and functional validation of the variant was performed in primary patient cells.

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).

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.