A homozygous splice-site variant in ZMYND10 causes primary ciliary dyskinesia with primary infertility in a Chinese family.

Primary ciliary dyskinesia (PCD) is a monogenic disorder of motile cilia characterized by impaired mucociliary clearance and multisystem involvement. We describe a patient with bronchiectasis, chronic rhinosinusitis, situs inversus, and primary infertility with hoard the ZMYND10 splice-site variant (NM_015896.4:c.511-1G>A). High-speed video microscopy (HSVM) demonstrated near-complete immotility of respiratory cilia. RT-PCR and cDNA sequencing revealed aberrant splicing with insertion of a 100-bp fragment, leading to a frameshift and a pre-mature termination codon predicted to trigger non-sense-mediated mRNA decay and truncate the C-terminal MYND domain. Consistently, ZMYND10 transcript and protein levels were markedly reduced. Transmission electron microscopy demonstrated loss of both outer and inner dynein arms. Concordantly, immunofluorescence showed absence of DNAH5, supporting an outer dynein arm defect. In addition, single-headed inner dynein arm components were selectively disrupted, as evidenced by loss of DNALI1, whereas the double-headed IDAf component DNAH2 was preserved. Notably, GAS8 (DRC4) was absent despite preserved DRC1 expression, suggesting that GAS8 loss in this case was not simply secondary to DRC1 deficiency and may reflect broader perturbation of nexin-dynein regulatory complex organization. Collectively, these findings expand the phenotypic spectrum and molecular characterization of ZMYND10-related PCD and provide further insight into dynein arm assembly and axonemal organization.