McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
Orphanet J Rare Dis. 2021 Jul 1;16(1):293. doi: 10.1186/s13023-021-01840-2.
Primary ciliary dyskinesia (PCD) is a rare, highly heterogeneous genetic disorder involving the impairment of motile cilia. With no single gold standard for PCD diagnosis and complicated multiorgan dysfunction, the diagnosis of PCD can be difficult in clinical settings. Some methods for diagnosis, such as nasal nitric oxide measurement and digital high-speed video microscopy with ciliary beat pattern analysis, can be expensive or unavailable. To confirm PCD diagnosis, we used a strategy combining assessment of typical symptoms with whole-exome sequencing (WES) and/or low-pass whole-genome sequencing (WGS) as an unbiased detection tool to identify known pathogenic mutations, novel variations, and copy number variations.
A total of 26 individuals of Chinese origin with a confirmed PCD diagnosis aged 13 to 61 years (median age, 24.5 years) were included. Biallelic pathogenic mutations were identified in 19 of the 26 patients, including 8 recorded HGMD mutations and 24 novel mutations. The detection rate reached 73.1%. DNAH5 was the most frequently mutated gene, and c.8383C > T was the most common mutated variant, but it is relatively rare in PCD patients from other ethnic groups.
This study demonstrates the practical clinical utility of combining WES and low-pass WGS as a no-bias detecting tool in adult patients with PCD, showing a clinical characteristics and genetic spectrum of Chinese PCD patients.
原发性纤毛运动障碍（PCD）是一种罕见的、高度异质性的遗传疾病，涉及到运动纤毛的功能障碍。由于没有单一的 PCD 诊断金标准，且多器官功能复杂，PCD 的临床诊断可能具有挑战性。一些诊断方法，如鼻一氧化氮测量和带有纤毛拍打模式分析的数字高速视频显微镜，可能昂贵或无法获得。为了确认 PCD 诊断，我们采用了一种策略，将典型症状评估与外显子组测序（WES）和/或低深度全基因组测序（WGS）相结合，作为一种无偏检测工具，以识别已知的致病性突变、新的变异和拷贝数变异。
共纳入 26 名确诊为 PCD 的中国血统患者，年龄 13 至 61 岁（中位数年龄为 24.5 岁）。26 名患者中有 19 名患者发现了双等位基因致病性突变，包括 8 个记录在 HGMD 中的突变和 24 个新突变。检测率达到 73.1%。DNAH5 是最常突变的基因，c.8383C>T 是最常见的突变变体，但在其他种族的 PCD 患者中相对较少见。
本研究表明，WES 和低深度 WGS 相结合作为一种无偏检测工具，在成年 PCD 患者中具有实际的临床应用价值，展示了中国 PCD 患者的临床特征和遗传谱。
