Diagnosis of primary ciliary dyskinesia (PCD) still remains a challenge, especially with mutations in the Dynein Arm Heavy Chain 11 (DNAH11) gene. Classical diagnostic measures like Transmission Electron Microscopy (TEM) are not applicable for mutations in the DNAH11 gene since ultrastructural defects of the ciliary apparatus are absent. Novel mutations encoding for PCD appear all the time with considerable variation in the clinical picture, making it necessary to update data bases and guidelines for PCD diagnostics. In this study we examined two unrelated, Finnish families with symptoms of PCD applying the clinical scoring system: Primary ciliary dyskinesia Rule (PICADAR), high speed video microscopy analysis (HSVMA) for ciliary movement, a commercially available gene panel analysis and nasal Nitric Oxide (nNO) measurements if applicable. Two, likely pathogenic variants in the DNAH11 gene (c.2341G > A, p. (Glu781Lys) ja c.7645 + 5G > A) were detected. In the first family, compound heterozygous mutations led to disease manifestation in two of 4 children, which showed a similar phenotype of cilia beating pattern but marked differences in disease severity. In the second family, all three children were homozygotes for the c.2341G > A p.(Glu781Lys) mutation and showed a similar degree of disease severity. However, the phenotype of cilia beating pattern was different ranging from stiff, static cilia to a hyperkinetic movement in one of these children. In this study we describe two Finnish families with PCD, revealing two novel mutations in the DNAH11 gene which show considerable variety in the clinical and beating cilia phenotype. The results of this study show the clinician that PCD can be much milder than generally expected and diagnosis demands a combination of measures which are only successful in experienced hands. Chronic and repeatedly treated wet cough should raise suspicion of PCD, referring the patient for further diagnostics to a specialised PCD centre.

中文翻译：

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原发性睫状运动障碍（CILD7）中DNAH11基因的两个新突变，在临床和跳动纤毛表型方面差异很大

诊断原发性睫状运动障碍（PCD）仍然是一个挑战，尤其是在Dynein Arm重链11（DNAH11）基因突变的情况下。像透射电子显微镜（TEM）这样的经典诊断方法不适用于DNAH11基因的突变，因为不存在睫状体的超微结构缺陷。编码PCD的新突变一直出现，临床情况也有相当大的变化，因此有必要更新数据库和PCD诊断指南。在这项研究中，我们使用临床评分系统检查了两个不相关的，具有PCD症状的芬兰家庭：原发性睫状运动障碍规则（PICADAR），用于睫状运动的高速视频显微镜分析（HSVMA），可商购的基因面板分析和一氧化氮鼻（nNO）测量（如果适用）。二，可能检测到了DNAH11基因的致病变异（c.2341G> A，p。（Glu781Lys）ja c.7645 + 5G> A）。在第一个家庭中，复合杂合突变导致4个孩子中的2个孩子出现疾病表现，这表现出相似的纤毛跳动表型，但疾病严重程度存在明显差异。在第二个家庭中，三个孩子均为c.2341G> A p。（Glu781Lys）突变的纯合子，并显示出相似的疾病严重程度。但是，这些孩子之一的纤毛跳动表型从僵硬的静态纤毛到运动过度而有所不同。在这项研究中，我们描述了两个带有PCD的芬兰家庭，揭示了DNAH11基因中的两个新突变，这些突变在临床和跳动纤毛表型方面表现出相当大的多样性。这项研究的结果表明，临床医生认为PCD可能比一般预期的要温和得多，并且诊断要求采取多种措施，这些措施只有在有经验的双手中才能成功。慢性咳嗽和反复治疗的湿咳应引起对PCD的怀疑，将患者转诊至专门的PCD中心。