Clinical characteristics and severity of primary ciliary dyskinesia caused by large homozygous deletion including exons 1-4 of DRC1: A multicenter retrospective cohort study.

BACKGROUND

Approximately half of primary ciliary dyskinesia (PCD) patients in Japan carry a large homozygous deletion encompassing exons 1-4 of DRC1 gene. However, the clinical manifestations of PCD patients with DRC1 variants remain poorly characterized.

METHODS

We conducted a multicenter retrospective cohort study at 12 hospitals across Japan. Patients with DRC1 variants were included, and their clinical characteristics, disease severity, and radiological features were compared with those of patients with outer dynein arm (ODA) defects.

RESULTS

A total of 43 patients with DRC1 variants and 21 with ODA defects were included. The median age at PCD diagnosis was 27 years (IQR: 17-41) for patients with DRC1 variants and 26 years (IQR: 8-31) for those with ODA defects. The median PICADAR score was significantly lower in patients with DRC1 variants than those with ODA defects (4 vs. 8, p < 0.001). The radiological severity and distribution of bronchiectasis did not differ between the two groups, while the median mucous plugging score (bronchiolitis/tree-in-bud) was significantly higher in patients with DRC1 variants (5, IQR: 4-6 vs. 3, IQR: 2-4, p = 0.044). In patients with DRC1 variants, the FEV1 z score was negatively correlated with age (r = -0.37, p = 0.028), and the modified Reiff score was positively correlated with age (r = 0.47, p = 0.010).

CONCLUSIONS

Although the sensitivity of the PICADAR score was low in these patients, most clinical and radiological features of DRC1-related PCD were relatively typical of PCD. Given that DRC1-related PCD appears to worsen with age, early diagnosis and timely intervention are crucial.