|Title||Cytoplasmic "ciliary inclusions" in isolation are not sufficient for the diagnosis of primary ciliary dyskinesia.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Vece, TJ, Sagel, SD, Zariwala, MA, Sullivan, KM, Burns, KA, Dutcher, SK, Yusupov, R, Leigh, MW, Knowles, MR|
|Date Published||2020 01|
|Keywords||Child, Preschool, Cilia, Ciliary Motility Disorders, Female, Genetic Testing, Humans, Infant, Male, Nasal Mucosa, Nitric Oxide, Whole Exome Sequencing|
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: "Ciliary Inclusions", in isolation, are not sufficient to diagnosis PCD. If seen, additional studies should be done to pursue an accurate diagnosis.
|Alternate Journal||Pediatr Pulmonol|
|PubMed Central ID||PMC7068840|
|Grant List||R01HL071798 / HL / NHLBI NIH HHS / United States |
U2C TR002818 / TR / NCATS NIH HHS / United States
5R01HL12837004 / HL / NHLBI NIH HHS / United States
UM1 HG006504 / HG / NHGRI NIH HHS / United States
U54 HL096458 / HL / NHLBI NIH HHS / United States
R01 HL071798 / HL / NHLBI NIH HHS / United States
U54HL096458 / HL / NHLBI NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States
R01 HL128370 / HL / NHLBI NIH HHS / United States
UL1 TR002535 / TR / NCATS NIH HHS / United States
UL1TR001082 / TR / NCATS NIH HHS / United States