Inner dynein arm defects causing primary ciliary dyskinesia: repeat testing required

O’Callaghan, Christopher; Rutman, Andrew; Williams, G; Hirst, Robert A.

doi:10.1183/09031936.00108410

Cited by 88 publications

(70 citation statements)

References 22 publications

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“…An isolated IDA defect was not diagnostic, as this can be nonspecific (19). PCD was confirmed by identification of biallelic DNAH11 mutations in patients with normal ultrastructure (20).…”

Section: Other Testsmentioning

confidence: 99%

Standardizing Nasal Nitric Oxide Measurement as a Test for Primary Ciliary Dyskinesia

Leigh¹,

Hazucha²,

Chawla³

et al. 2013

Annals ATS

241

289

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Rationale: Several studies suggest that nasal nitric oxide (nNO) measurement could be a test for primary ciliary dyskinesia (PCD), but the procedure and interpretation have not been standardized.Objectives: To use a standard protocol for measuring nNO to establish a diseasespecific cutoff value at one site, and then validate at six other sites.Methods: At the lead site, nNO was prospectively measured in individuals later confirmed to have PCD by ciliary ultrastructural defects (n = 143) or DNAH11 mutations (n = 6); and in 78 healthy and 146 disease control subjects, including individuals with asthma (n = 37), cystic fibrosis (n = 77), and chronic obstructive pulmonary disease (n = 32). A disease-specific cutoff value was determined, using generalized estimating equations (GEEs). Six other sites prospectively measured nNO in 155 consecutive individuals enrolled for evaluation for possible PCD. Measurements and Main Results:At the lead site, nNO values in PCD (mean 6 standard deviation, 20.7 6 24.1 nl/min; range, 1.5-207.3 nl/min) only rarely overlapped with the nNO values of healthy control subjects (304.6 6 118.8; 125.5-867.0 nl/min), asthma (267.8 6 103.2; 125.0-589.7 nl/min), or chronic obstructive pulmonary disease (223.7 6 87.1; 109.7-449.1 nl/min); however, there was overlap with cystic fibrosis (134.0 6 73.5; 15.6-386.1 nl/min). The disease-specific nNO cutoff value was defined at 77 nl/minute (sensitivity, 0.98; specificity, .0.999). At six other sites, this cutoff identified 70 of the 71 (98.6%) participants with confirmed PCD.Conclusions: Using a standardized protocol in multicenter studies, nNO measurement accurately identifies individuals with PCD, and supports its usefulness as a test to support the clinical diagnosis of PCD.

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“…An isolated IDA defect was not diagnostic, as this can be nonspecific (19). PCD was confirmed by identification of biallelic DNAH11 mutations in patients with normal ultrastructure (20).…”

Section: Other Testsmentioning

confidence: 99%

Standardizing Nasal Nitric Oxide Measurement as a Test for Primary Ciliary Dyskinesia

Leigh¹,

Hazucha²,

Chawla³

et al. 2013

Annals ATS

241

289

View full text Add to dashboard Cite

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“…The results of these investigations are shown in Table 1. on a repeat sample obtained from a primary cell culture in the absence of infective and inflammatory stimuli [7]. These findings suggest an absence of IDA shown by TEM may not be sufficient to confirm a diagnosis of PCD.…”

Section: Resultsmentioning

confidence: 75%

“…IMOD was used to average each of the microtubule doublets [1][2][3][4][5][6][7][8][9] from nine individual axonemal cross sections. This helped to remove noise and enhance the quality of the IDA structures.…”

Section: Central Pairmentioning

confidence: 99%

Inner Dynein Arm Defects in Primary Ciliary Dyskinesia

Shoemark¹

2013

J Genet Syndr Gene Ther

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Primary ciliary dyskinesia (PCD) is a genetic condition in which there is a defect in cilia motility. This can be caused by the absence of the inner dynein arm motor (IDA). The IDA can be difficult to observe by electron microscopy and has been shown to transiently disappear, making accurate diagnosis difficult.This study reviewed cases of PCD due to an IDA defect on the Royal Brompton Hospital database in order to confirm or retract the diagnosis. This was achieved using current methods of diagnosis (nasal nitric oxide, light and electron microscopy) and new techniques to improve visualisation of the IDA such as immunofluorescence analysis and 3D electron tomography.

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“…IDA defects associated with microtubular disorganisation occur in 15% of PCD, but isolated IDA defects as a cause of PCD are controversial particularly as no mutations have been identified in IDA proteins. IDA are difficult to identify due to the decreased repeats along the ciliary axoneme compared to the ODA [60] therefore false positive IDA defects are likely. Reporting of isolated IDA defects requires repeated testing or immunofluorescence staining of the IDA visualizing the entire axoneme [60].…”

Section: Page 5 Of 36mentioning

confidence: 99%

“…IDA are difficult to identify due to the decreased repeats along the ciliary axoneme compared to the ODA [60] therefore false positive IDA defects are likely. Reporting of isolated IDA defects requires repeated testing or immunofluorescence staining of the IDA visualizing the entire axoneme [60]. Central pair defects occur less frequently (5-15%) and are associated with a mix of both normal and abnormal cilia [61,62], therefore adequate numbers of cilia need to be viewed in longitudinal and transverse section; in the author's laboratory at least 100 and up to 300 cilia selected from healthy cells are analysed in transverse section.…”

Section: Page 5 Of 36mentioning

confidence: 99%

Diagnostic Methods in Primary Ciliary Dyskinesia

Lucas

Paff

Goggin

et al. 2016

Paediatric Respiratory Reviews

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Educational Aims; The reader will be able to; Describe the basis of the various diagnostic tests for PCD  Have an understanding of the strengths and limitations of each test  Understand that there is no 'gold standard' test  Understand why highly specialised centres should analyse samples and interpret results. Page 2 of 36A c c e p t e d M a n u s c r i p t  SummaryDiagnosing primary ciliary dyskinesia is difficult. With no reference standard, a combination of tests is needed; most tests require expensive equipment and specialist scientists. We review the advances in diagnostic testing over the past hundred years, with emphasis on recent advances.We particularly focus on use of high-speed video analysis, transmission electron microscopy, nasal nitric oxide and genetic testing. We discuss the international efforts that are in place to advance the evidence base for diagnostic tests.

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Inner dynein arm defects causing primary ciliary dyskinesia: repeat testing required

Abstract: Primary ciliary dyskinesia (PCD) results in chronic nasal symptoms and chest disease leading to bronchiectasis. We noted a number of patients referred for diagnostic testing whose initial results suggested PCD

Cited by 88 publications

References 22 publications

Standardizing Nasal Nitric Oxide Measurement as a Test for Primary Ciliary Dyskinesia

Standardizing Nasal Nitric Oxide Measurement as a Test for Primary Ciliary Dyskinesia

Inner Dynein Arm Defects in Primary Ciliary Dyskinesia

Diagnostic Methods in Primary Ciliary Dyskinesia

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