Unlike disorders of primary cilium, primary ciliary dyskinesia (PCD) has a much narrower clinical spectrum consistent with the limited tissue distribution of motile cilia. Nonetheless, PCD diagnosis can be challenging due to the overlapping features with other disorders and the requirement for sophisticated tests that are only available in specialized centers. We performed exome sequencing on all patients with a clinical suspicion of PCD but for whom no nasal nitric oxide test or ciliary functional assessment could be ordered. Among 81 patients (56 families), in whom PCD was suspected, 68% had pathogenic or likely pathogenic variants in established PCD-related genes that fully explain the phenotype (20 variants in 11 genes). The major clinical presentations were sinopulmonary infections (SPI) (n = 58), neonatal respiratory distress (NRD) (n = 2), laterality defect (LD) (n = 6), and combined LD/SPI (n = 15). Biallelic likely deleterious variants were also encountered in AKNA and GOLGA3, which we propose as novel candidates in a lung phenotype that overlaps clinically with PCD. We also encountered a PCD phenocopy caused by a pathogenic variant in ITCH, and a pathogenic variant in CEP164 causing Bardet-Biedl syndrome and PCD presentation as a very rare example of the dual presentation of these two disorders of the primary and motile cilia. Exome sequencing is a powerful tool that can help "democratize" the diagnosis of PCD, which is currently limited to highly specialized centers.

中文翻译：

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一种以外显子组为先的方法来辅助诊断原发性睫状运动障碍。

与原发性纤毛症不同，原发性睫状运动障碍（PCD）具有较窄的临床频谱，与活动性纤毛的有限组织分布相一致。尽管如此，由于与其他疾病的重叠特征以及仅在专门中心才可以进行的复杂检查的要求，PCD诊断仍然具有挑战性。我们对所有临床上怀疑患有PCD的患者进行了外显子组测序，但对于这些患者，无须进行鼻腔一氧化氮测试或睫状功能评估。在怀疑患有PCD的81位患者（56个家庭）中，有68％的患者在已建立的PCD相关基因中具有致病性或可能的致病性变体，这些变体充分解释了表型（11个基因中有20个变体）。主要临床表现为肺肺感染（SPI）（n = 58），新生儿呼吸窘迫（NRD）（n = 2），侧向缺陷（LD）（n = 6）和LD / SPI组合（n = 15）。在AKNA和GOLGA3中也遇到了双等位基因可能有害的变体，我们建议将其作为与PCD临床重叠的肺表型的新候选者。我们还遇到了由ITCH中的致病变异引起的PCD表型，以及引起Bardet-Biedl综合征和PCD表现的CEP164中的致病变异，这是原发性和活动性纤毛这两种疾病双重呈现的非常罕见的例子。外显子组测序是一种功能强大的工具，可以帮助“民主化” PCD的诊断，目前仅限于高度专业化的中心。我们建议将其作为与PCD临床重叠的肺表型的新型候选药物。我们还遇到了由ITCH中的病原体变异引起的PCD表型，以及引起Bardet-Biedl综合征和PCD表现的CEP164中的病原体变异，这是原发性和活动性纤毛这两种疾病双重呈现的非常罕见的例子。外显子组测序是一种功能强大的工具，可以帮助“民主化” PCD的诊断，目前仅限于高度专业化的中心。我们建议将其作为与PCD临床重叠的肺表型的新型候选药物。我们还遇到了由ITCH中的致病变异引起的PCD表型，以及引起Bardet-Biedl综合征和PCD表现的CEP164中的致病变异，这是原发性和活动性纤毛这两种疾病双重呈现的非常罕见的例子。外显子组测序是一种功能强大的工具，可以帮助“民主化” PCD的诊断，而PCD的诊断目前仅限于高度专业的中心。