Diagnostic utility of standardized assessment of ciliary ultrastructure by transmission electron microscopy in primary ciliary dyskinesia: a Japanese perspective.

BACKGROUND

Primary ciliary dyskinesia (PCD) is a rare genetic disorder associated with structural or functional ciliary defects. Its diagnosis usually requires a combination of tests, including observation of the cilium structure by transmission electron microscopy (TEM). In Japan, when TEM was previously the primary method for diagnosing PCD, there were no standardized methods for evaluating TEM findings, and the correlations with PCD-causing genes remained unclear.

METHODS

Here, we evaluated 101 patients with suspected PCD using a standardized assessment of ciliary ultrastructure by TEM, based on the international guidelines that classify defects into Class 1 and Class 2.

RESULTS

Class 1 or 2 ciliary defects on TEM were identified in 27 patients (26.7 %); Class 1 defects (n = 19) correlated well with the genotypes in Japanese patients with PCD, most commonly caused by DNAH5 and CCDC39/40. TEM proved valuable as a complementary tool, when genetic testing failed to yield a definitive diagnosis, particularly in cases where two heterozygous variants of unknown phase were identified in a single PCD-causing gene. It was especially informative in PCD patients with situs inversus. However, in cases involving homozygous DRC1 variants, which are most frequently identified among Japanese patients with PCD, only subtle ultrastructural defects were observed, highlighting the limitations of TEM as a standalone diagnostic method. Our study also demonstrated the need for and effectiveness of standardizing the assessment of ciliary ultrastructure by TEM.

CONCLUSIONS

The results of this study provide a crucial foundation for establishing a better TEM-based diagnostic system in Japan.