|Title||Laterality defects other than situs inversus totalis in primary ciliary dyskinesia: insights into situs ambiguus and heterotaxy.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Shapiro, AJ, Davis, SD, Ferkol, T, Dell, SD, Rosenfeld, M, Olivier, KN, Sagel, SD, Milla, C, Zariwala, MA, Wolf, W, Carson, JL, Hazucha, MJ, Burns, K, Robinson, B, Knowles, MR, Leigh, MW|
|Corporate Authors||Genetic Disorders of Mucociliary Clearance Consortium|
|Date Published||2014 Nov|
|Keywords||Adolescent, Adult, Biopsy, Child, Child, Preschool, Cilia, DNA, DNA Mutational Analysis, Female, Humans, Infant, Infant, Newborn, Kartagener Syndrome, Male, Microscopy, Electron, Transmission, Middle Aged, Mutation, Prevalence, Prospective Studies, Tomography, X-Ray Computed, United States, Young Adult|
BACKGROUND: Motile cilia dysfunction causes primary ciliary dyskinesia (PCD), situs inversus totalis (SI), and a spectrum of laterality defects, yet the prevalence of laterality defects other than SI in PCD has not been prospectively studied.
METHODS: In this prospective study, participants with suspected PCD were referred to our multisite consortium. We measured nasal nitric oxide (nNO) level, examined cilia with electron microscopy, and analyzed PCD-causing gene mutations. Situs was classified as (1) situs solitus (SS), (2) SI, or (3) situs ambiguus (SA), including heterotaxy. Participants with hallmark electron microscopic defects, biallelic gene mutations, or both were considered to have classic PCD.
RESULTS: Of 767 participants (median age, 8.1 years, range, 0.1-58 years), classic PCD was defined in 305, including 143 (46.9%), 125 (41.0%), and 37 (12.1%) with SS, SI, and SA, respectively. A spectrum of laterality defects was identified with classic PCD, including 2.6% and 2.3% with SA plus complex or simple cardiac defects, respectively; 4.6% with SA but no cardiac defect; and 2.6% with an isolated possible laterality defect. Participants with SA and classic PCD had a higher prevalence of PCD-associated respiratory symptoms vs SA control participants (year-round wet cough, P
CONCLUSIONS: At least 12.1% of patients with classic PCD have SA and laterality defects ranging from classic heterotaxy to subtle laterality defects. Specific clinical features of PCD and low nNO levels help to identify PCD in patients with laterality defects.
TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00323167; URL: www.clinicaltrials.gov.
|PubMed Central ID||PMC4219335|
|Grant List||UL1TR000154 / TR / NCATS NIH HHS / United States |
UL1TR000423 / TR / NCATS NIH HHS / United States
UL1TR000083 / TR / NCATS NIH HHS / United States
5R01HL071798 / HL / NHLBI NIH HHS / United States
UL1 TR000154 / TR / NCATS NIH HHS / United States
U54 HL096458 / HL / NHLBI NIH HHS / United States
U54HL096458 / HL / NHLBI NIH HHS / United States
U54 HG006504 / HG / NHGRI NIH HHS / United States
R01 HL071798 / HL / NHLBI NIH HHS / United States
UL1 TR000083 / TR / NCATS NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States
UL1 TR000423 / TR / NCATS NIH HHS / United States
5US54HL096458-06 / HL / NHLBI NIH HHS / United States