Tampere University Hospital, Allergy Centre, PB 2000, 33521, Tampere, Finland.
Department of Pediatrics, Turku University Hospital, Kiinanmyllynkatu 4-8, 20520, Turku, Finland.
BMC Med Genet. 2020 Nov 26;21(1):237. doi: 10.1186/s12881-020-01171-2.
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.
原发性纤毛运动障碍（PCD）的诊断仍然具有挑战性，特别是在 Dynein Arm Heavy Chain 11（DNAH11）基因发生突变的情况下。经典的诊断措施，如透射电子显微镜（TEM），不适用于 DNAH11 基因突变，因为纤毛器的超微结构缺陷不存在。新型突变不断出现，PCD 的临床表现差异很大，因此有必要更新 PCD 诊断的数据和指南。
在这项研究中，我们应用临床评分系统：原发性纤毛运动障碍规则（PICADAR）、高速视频显微镜分析（HSVMA）分析纤毛运动、商业可用的基因panel 分析以及鼻一氧化氮（nNO）测量（如果适用），检查了两个具有 PCD 症状的芬兰无关家族。
在第一个家族中，发现了 DNAH11 基因中的两个可能的致病性变异（c.2341G>A，p.（Glu781Lys）和 c.7645+5G>A）。在第一个家族中，复合杂合突变导致 4 个孩子中的 2 个发病，其纤毛跳动模式表现出相似的表型，但疾病严重程度有明显差异。在第二个家族中，所有三个孩子均为 c.2341G>A p.（Glu781Lys）突变的纯合子，疾病严重程度相似。然而，纤毛跳动模式的表型不同，从僵硬、静态的纤毛到其中一个孩子的过度活跃运动。
在这项研究中，我们描述了两个芬兰的 PCD 家族，揭示了 DNAH11 基因中的两个新突变，这些突变在临床和纤毛跳动表型方面表现出相当大的差异。这项研究的结果表明，PCD 可能比一般预期的要轻得多，诊断需要一系列措施的结合，只有在经验丰富的手中才能成功。慢性和反复治疗的湿咳应引起对 PCD 的怀疑，将患者转介到专门的 PCD 中心进行进一步诊断。
