Cytoplasmic "ciliary inclusions" in isolation are not sufficient for the diagnosis of primary ciliary dyskinesia.
cilia EM
ciliary inclusions
primary ciliary dyskinesia
Journal
Pediatric pulmonology
ISSN: 1099-0496
Titre abrégé: Pediatr Pulmonol
Pays: United States
ID NLM: 8510590
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
28
05
2019
accepted:
01
09
2019
pubmed:
25
9
2019
medline:
25
8
2020
entrez:
25
9
2019
Statut:
ppublish
Résumé
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.
Sections du résumé
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.
Identifiants
pubmed: 31549486
doi: 10.1002/ppul.24528
pmc: PMC7068840
mid: NIHMS1562811
doi:
Substances chimiques
Nitric Oxide
31C4KY9ESH
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
130-135Subventions
Organisme : NHLBI NIH HHS
ID : R01HL071798
Pays : United States
Organisme : NCATS NIH HHS
ID : U2C TR002818
Pays : United States
Organisme : NHLBI NIH HHS
ID : 5R01HL12837004
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006504
Pays : United States
Organisme : NHLBI NIH HHS
ID : U54 HL096458
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL071798
Pays : United States
Organisme : NHLBI NIH HHS
ID : U54HL096458
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001082
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128370
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002535
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1TR001082
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 Wiley Periodicals, Inc.
Références
Adv Pediatr. 1988;35:139-65
pubmed: 3055856
Am J Hum Genet. 2019 Feb 7;104(2):229-245
pubmed: 30665704
Chest. 2010 Dec;138(6):1441-7
pubmed: 20616212
N Engl J Med. 1977 Jul 7;297(1):1-6
pubmed: 301245
Am J Respir Crit Care Med. 2004 Feb 15;169(4):459-67
pubmed: 14656747
J Med Genet. 2003 Aug;40(8):575-84
pubmed: 12920066
Pediatr Pulmonol. 2016 Feb;51(2):115-32
pubmed: 26418604
Am J Respir Crit Care Med. 2018 Jun 15;197(12):e24-e39
pubmed: 29905515
Nat Commun. 2014 Jul 22;5:4418
pubmed: 25048963
Ultrastruct Pathol. 2017 Nov-Dec;41(6):390-398
pubmed: 28922056
Ann Am Thorac Soc. 2013 Dec;10(6):574-81
pubmed: 24024753
Eur Respir J. 2009 Aug;34(2):401-4
pubmed: 19648518
Ultrastruct Pathol. 1994 May-Jun;18(3):327-32
pubmed: 8066823
Chest. 2012 Aug;142(2):543-544
pubmed: 22871779
Annu Rev Physiol. 2015;77:379-406
pubmed: 25386990
Eur Respir J. 2001 Dec;18(6):965-70
pubmed: 11829103
Ann Am Thorac Soc. 2016 Aug;13(8):1305-13
pubmed: 27070726
Pediatr Res. 2017 Mar;81(3):398-405
pubmed: 27935903
Am J Respir Crit Care Med. 1996 Mar;153(3):1123-9
pubmed: 8630555
Ultrastruct Pathol. 2000 May-Jun;24(3):169-74
pubmed: 10914428
Thorax. 2012 May;67(5):433-41
pubmed: 22184204
Nat Genet. 2014 Jun;46(6):646-51
pubmed: 24747639
Eur Respir J. 2011 Sep;38(3):603-7
pubmed: 21406509
Pediatr Dev Pathol. 2014 Nov-Dec;17(6):465-9
pubmed: 25299134
Science. 1976 Jul 23;193(4250):317-9
pubmed: 1084576
Lancet. 1981 Aug 29;2(8244):476
pubmed: 6115234
J Allergy Clin Immunol. 2010 Oct;126(4):722-729.e2
pubmed: 20673980