Clinical and molecular insights into primary ciliary dyskinesia: Genotype-phenotype correlation and protein interaction networks in an Indian retrospective cohort.

Background

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Objective

Primary ciliary dyskinesia (PCD) is a rare genetic disorder causing defective ciliary motility, leading to chronic respiratory disease, neonatal distress, subfertility, and laterality defects. This study examines the clinical and genetic spectrum of PCD in a South Asian cohort, focusing on genotype-phenotype correlations, protein interaction effects of pathogenic variants, and the role of bioinformatics in improving molecular diagnosis.

Methods

We conducted a retrospective study of suspected PCD cases at a tertiary referral centre in India from 2017 to 2025, reviewing clinical, laboratory, imaging, and exome sequencing data. Protein-protein interaction (PPI) and Gene Ontology (GO) enrichment analyses were performed to assess functional convergence.

Results

Out of 41 individuals suspected of having PCD, 31 were molecularly confirmed. Most cases presented in childhood, while a subset presented in adulthood, often primarily with infertility. Pathogenic or likely pathogenic variants were identified in 18 genes associated with PCD, with the most common being DNAH11, DNAH9, DNAH5, and CCDC40; homozygous variants were predominant. Structural modelling indicated the preservation of global protein folds, with localised conformational deviations noted particularly in DNAH5 and DNAH11 . PPI network analysis revealed significant interaction enrichment ( P < 1 × 10 -16 ). GO analysis showed strong enrichment of cilia-related biological processes, including microtubule-based processes (-log 10 FDR = 22.96) and microtubule bundle formation (-log 10 FDR = 27.54).

Conclusions

This study enhances understanding of PCD variants in the Indian population and highlights the value of combining clinical evaluations with genomic and structural analyses. PPI and GO analyses reveal disrupted ciliary pathways linked to PCD.