Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.

原发性纤毛运动障碍 (PCD) 是一种先天性运动性纤毛病，具有多效性症状。尽管已经确定了近 50 个致病基因，但它们仅占明确 PCD 病例的大约 70%。动力蛋白轴丝重链 10 ( DNAH10 ) 编码运动纤毛和精子鞭毛中内臂动力蛋白重链的一个亚基。基于运动纤毛和精子鞭毛的共同轴丝结构，DNAH10变体很可能导致 PCD。使用外显子组测序，我们在来自近亲家庭的 PCD 患者中发现了一个新的DNAH10纯合变体 (c.589C > T, p.R197W)。患者表现为鼻窦炎、支气管扩张、内脏反位和弱畸精子症。免疫染色分析显示不存在DNAH10和DNALI1在呼吸纤毛中，透射电子显微镜显示呼吸纤毛和精子鞭毛中的轴丝 9+2 结构明显紊乱和内动力蛋白臂缺陷。随后，携带错义变异的Dnah10基因敲入小鼠和Dnah10基因敲除小鼠的动物模型重现了 PCD 的表型，包括慢性呼吸道感染、男性不育症和脑积水。据我们所知，这项研究首次报告了人类和小鼠模型中与 PCD 相关的DNAH10缺陷，这表明DNAH10隐性突变是 PCD 的病因。