TY - JOUR
T1 - Laterality Defects in Primary Ciliary Dyskinesia
T2 - Relationship to Ultrastructural Defect or Genotype
AU - Genetic Disorders of Mucociliary Clearance Consortium (GDMCC)
AU - Barber, Andrew T.
AU - Shapiro, Adam J.
AU - Davis, Stephanie D.
AU - Ferkol, Thomas W.
AU - Atkinson, Jeffrey J.
AU - Sagel, Scott D.
AU - Dell, Sharon D.
AU - Olivier, Kenneth N.
AU - Milla, Carlos E.
AU - Rosenfeld, Margaret
AU - Li, Lang
AU - Lin, Feng Chang
AU - Sullivan, Kelli M.
AU - Capps, Nicole A.
AU - Zariwala, Maimoona A.
AU - Knowles, Michael R.
AU - Leigh, Margaret W.
N1 - Publisher Copyright:
Copyright © 2023 by the American Thoracic Society.
PY - 2023/3
Y1 - 2023/3
N2 - Rationale: The association between organ laterality abnormalities and ciliary ultrastructural defect or genotype in primary ciliary dyskinesia is poorly understood. Objectives: To determine if there is an association between presence and/or type of laterality abnormality and ciliary ultrastructural defect or genotype. Methods: Participants with primary ciliary dyskinesia in a multicenter, prospective study were grouped based on ciliary ultrastructural defect or genotype. In a retrospective analysis of these 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. Results: 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 with the group with inner dynein arm defects with microtubular disorganization, laterality defects were more likely in the outer dynein arm defects group (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.21–3.54; P, 0.01) and less likely in the normal/near normal ultrastructure group (OR, 0.04; 95% CI, 0.013–0.151; P, 0.01). Heterotaxy was present in 11 of 242 (4.5%) in the outer dynein arm defects group but 0 of 96 in the inner dynein arm defects with microtubular disorganization group (P = 0.038). Conclusion: In primary ciliary dyskinesia, risk of a laterality abnormality differs by ciliary ultrastructural defect. Pathophysiologic mechanisms underlying these differences require further exploration.
AB - Rationale: The association between organ laterality abnormalities and ciliary ultrastructural defect or genotype in primary ciliary dyskinesia is poorly understood. Objectives: To determine if there is an association between presence and/or type of laterality abnormality and ciliary ultrastructural defect or genotype. Methods: Participants with primary ciliary dyskinesia in a multicenter, prospective study were grouped based on ciliary ultrastructural defect or genotype. In a retrospective analysis of these 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. Results: 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 with the group with inner dynein arm defects with microtubular disorganization, laterality defects were more likely in the outer dynein arm defects group (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.21–3.54; P, 0.01) and less likely in the normal/near normal ultrastructure group (OR, 0.04; 95% CI, 0.013–0.151; P, 0.01). Heterotaxy was present in 11 of 242 (4.5%) in the outer dynein arm defects group but 0 of 96 in the inner dynein arm defects with microtubular disorganization group (P = 0.038). Conclusion: In primary ciliary dyskinesia, risk of a laterality abnormality differs by ciliary ultrastructural defect. Pathophysiologic mechanisms underlying these differences require further exploration.
KW - laterality
KW - situs ambiguous
KW - situs inversus totalis
UR - http://www.scopus.com/inward/record.url?scp=85149167009&partnerID=8YFLogxK
U2 - 10.1513/AnnalsATS.202206-487OC
DO - 10.1513/AnnalsATS.202206-487OC
M3 - Article
C2 - 36342963
AN - SCOPUS:85149167009
SN - 2329-6933
VL - 20
SP - 397
EP - 405
JO - Annals of the American Thoracic Society
JF - Annals of the American Thoracic Society
IS - 3
ER -