Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina.
Department of Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado.
Pediatr Pulmonol. 2020 Jan;55(1):130-135. doi: 10.1002/ppul.24528. Epub 2019 Sep 23.
The diagnosis of primary ciliary dyskinesia (PCD) is difficult and requires a combination of clinical features, nasal nitric oxide testing, cilia ultrastructural analysis by electron microscopy (EM), and genetics. A recently described cytoplasmic ultrastructural change termed "ciliary inclusions" was reported to be diagnostic of PCD; however, no supporting evidence of PCD was provided. In this study, we sought to confirm, or refute, the diagnosis of PCD in subjects with "ciliary inclusions" on EM.
Six subjects from five families with previous lab reports of "ciliary inclusions" on EMs of ciliated cells were identified and evaluated at a Genetic Disorders of Mucociliary Clearance Consortium site. We performed a detailed clinical history, nasal nitric oxide measurement, genetic testing including whole-exome sequencing (WES), and when possible, repeat ciliary EM study.
Only one of six subjects had multiple and persistent clinical features congruent with PCD. No subject had situs inversus. Only one of six subjects had a very low nasal nitric oxide level. No "ciliary inclusions" were found in three subjects who had a repeat ciliary EM, and ciliary axonemal ultrastructures were normal. Genetic testing, including WES, was negative for PCD-causing genes, and for pathogenic variants in gene pathways that might cause "ciliary inclusions," such as ciliary biogenesis.
"Ciliary Inclusions", in isolation, are not sufficient to diagnosis PCD. If seen, additional studies should be done to pursue an accurate diagnosis.
原发性纤毛运动障碍（PCD）的诊断较为困难，需要结合临床特征、鼻一氧化氮检测、电子显微镜（EM）下的纤毛超微结构分析以及遗传学检查。最近描述了一种称为“纤毛包涵体”的细胞质超微结构改变，被认为是 PCD 的诊断指标；然而，并未提供支持 PCD 的证据。在这项研究中，我们试图在 EM 下具有“纤毛包涵体”的受试者中确认或反驳 PCD 的诊断。
从五个家族的六名先前报告 EM 下的纤毛细胞存在“纤毛包涵体”的受试者中确定并评估了六个主题，并在遗传障碍黏液清除综合征协作组（Genetic Disorders of Mucociliary Clearance Consortium）中进行了评估。我们进行了详细的临床病史、鼻一氧化氮测量、包括全外显子组测序（WES）在内的基因检测，并且在可能的情况下，重复了纤毛 EM 研究。
六名受试者中只有一名有多个持续存在的临床特征，与 PCD 相符。没有受试者有内脏转位。只有一名受试者的鼻一氧化氮水平非常低。在三名重复纤毛 EM 的受试者中均未发现“纤毛包涵体”，并且纤毛轴丝超微结构正常。基因检测，包括 WES，未发现 PCD 致病基因以及可能导致“纤毛包涵体”的基因通路的致病性变异，例如纤毛发生。
孤立的“纤毛包涵体”不足以诊断 PCD。如果发现，应进行更多研究以明确诊断。
