Back to Search Start Over

Laterality Defects in Primary Ciliary Dyskinesia: Relationship to Ultrastructural Defect or Genotype

Authors :
Andrew T. Barber
Adam J. Shapiro
Stephanie D. Davis
Thomas W. Ferkol
Jeffrey J. Atkinson
Scott D. Sagel
Sharon D. Dell
Kenneth N. Olivier
Carlos E. Milla
Margaret Rosenfeld
Lang Li
Feng-Chang Lin
Kelli M. Sullivan
Nicole A. Capps
Maimoona A. Zariwala
Michael R. Knowles
Margaret W. Leigh
Source :
Annals of the American Thoracic Society. 20:397-405
Publication Year :
2023
Publisher :
American Thoracic Society, 2023.

Abstract

The association between organ laterality abnormalities and ciliary ultrastructural defect or genotype in primary ciliary dyskinesia is poorly understood.To determine if there is an association between presence/type of laterality abnormality and ciliary ultrastructural defect and genotype.Participants with primary ciliary dyskinesia in a multicenter, prospective study were grouped based on ciliary ultrastructural defect or genotype. In a retrospective analysis of this data, the association of ciliary ultrastructural defect or genotype and likelihood of a laterality abnormality was evaluated by logistic regression adjusted for presence of two loss-of-function versus one or more not-loss-of-function variants.Of 559 participants, 286 (51.2%), 215 (38.5%), and 58 (10.4%) were identified as having situs solitus, situs inversus totalis, and situs ambiguus, respectively; heterotaxy, defined as situs ambiguus with complex cardiovascular defects, was present in 14 (2.5%). Compared to group with inner dynein arm defects with microtubular disorganization, laterality defects were more likely in the outer dynein arm defects group (OR 2.07, 95% CI 1.21-3.54, P0.01) and less likely in the normal/near normal ultrastructure group (OR 0.04, 95% CI 0.013-0.151, P0.01). Heterotaxy was present in 11 of 242 (4.5%) in the outer dynein arm defects group but zero of 96 in the inner dynein arm defects with microtubular disorganization group (P=0.038).In primary ciliary dyskinesia, risk of a laterality abnormality differs by ciliary ultrastructure defect. Pathophysiologic mechanisms underlying these differences require further exploration.

Details

ISSN :
23256621 and 23296933
Volume :
20
Database :
OpenAIRE
Journal :
Annals of the American Thoracic Society
Accession number :
edsair.doi.dedup.....e98b324634872e405094b9acc2bedfe0
Full Text :
https://doi.org/10.1513/annalsats.202206-487oc