MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia

Boon, Mieke; Wallmeier, Julia; Ma, Lina; Loges, Niki T.; Jaspers, Martine; Olbrich, Heike; Dougherty, Gerard W.; Raidt, Johanna; Werner, Claudius; Amirav, Israel; Hevroni, Avigdor; Abitbul, Revital; Avital, Avraham; Soferman, Ruth; Wessels, Marja W.; O’Callaghan, Christopher; Chung, Eddie M.K.; Rutman, Andrew; Hirst, Robert A.; Moya, Eduardo; Mitchison, Hannah M.; daele, Sabine Van; Boeck, K. De; Jorissen, Mark; Kintner, Chris; Cuppens, Harry; Omran, Heymut

doi:10.1038/ncomms5418

Cited by 225 publications

(249 citation statements)

References 18 publications

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“…There are now over thirty known genes responsible for >60% of cases. Recent publication of mutations in genes causing reduced numbers of cilia with normal motility and ultrastructure [13,14] in patients with a PCD phenotype, brings to question whether yet another change of name is required. Gene panels are now used as part of the diagnostic pathway in a number of countries.…”

Section: History Of Pcd Diagnostic Testingmentioning

confidence: 99%

“…For example, defects of nexin link components [63], central pair components [64], ciliary biogenesis defects [14] and defects caused by DNAH11 [65,66], usually cannot be visualized by classic TEM. Thus, normal ultrastructure cannot rule out PCD.…”

Section: Page 5 Of 36mentioning

confidence: 99%

“…Some genotype-phenotype relations have been described, but caution needs to be kept as some descriptions are based on low numbers of patients: mutations causing reduced generation of multiple motile cilia (MCIDAS, CCNO) and those causing IDA with microtubular disorganization (CCDC39, CCDC40) have been reported to result in relatively severe lung disease [13,14,68]. In contrast, mutations in RSPH1 (a mutation in a gene coding for one of the radial spoke subunits) reportedly cause a mild phenotype [69].…”

Section: Genetics: Pcd Is Generally An Autosomal Recessive Disease Tmentioning

confidence: 99%

“…Male patients with mutations in CCDC114 (coding for a docking protein for the ODA) are generally fertile [70]. Situs abnormalities are not observed in patients with mutations affecting the central pair [64] or radial spokes [49,50,69], nor in patients with reduced generation of multiple motile cilia [13,14]. However, it is likely that variable clinical pictures occur between patients with different mutations within a particular gene and even between patients with identical mutations.…”

Section: Genetics: Pcd Is Generally An Autosomal Recessive Disease Tmentioning

confidence: 99%

“…Recently, two genetic defects have been identified in patients previously classified as ciliary aplasia: mutations in CCNO and MCIDAS [13,14]. Mutations in CCNO and MCIDAS result in defective centriole generation and placement on the outer surface of the epithelial membrane.…”

Section: Genetics: Pcd Is Generally An Autosomal Recessive Disease Tmentioning

confidence: 99%

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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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Section: History Of Pcd Diagnostic Testingmentioning

confidence: 99%

Section: Page 5 Of 36mentioning

confidence: 99%

Section: Genetics: Pcd Is Generally An Autosomal Recessive Disease Tmentioning

confidence: 99%

Section: Genetics: Pcd Is Generally An Autosomal Recessive Disease Tmentioning

confidence: 99%

Section: Genetics: Pcd Is Generally An Autosomal Recessive Disease Tmentioning

confidence: 99%

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Diagnostic Methods in Primary Ciliary Dyskinesia

Lucas

Paff

Goggin

et al. 2016

Paediatric Respiratory Reviews

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Advances in the Diagnosis and Treatment of Primary Ciliary Dyskinesia

Dunsky

Menezes

Ferkol

2021

JAMA Otolaryngol Head Neck Surg

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IMPORTANCE Primary ciliary dyskinesia (PCD) is a rare, inherited condition involving motile cilia that line the upper and lower respiratory tracts, leading to chronic infections of the paranasal sinuses, middle ear, and bronchi that begin during infancy. Unfortunately, despite its early presentation, PCD is often recognized late.OBSERVATIONS People with PCD have diverse clinical manifestations, including chronic upper and lower respiratory tract disease, laterality defects, and subfertility. Through efforts of multinational clinical collaboratives, 4 cardinal features have been described that identify people who likely have PCD: unexplained neonatal respiratory distress, left-right laterality defects, daily wet cough, and nonseasonal rhinosinusitis beginning before 6 months of age. Recent advances in the understanding of the genetics and pathogenesis of the disease have led to a revolution in the approach to screening and diagnostic testing. Moreover, PCD has a broad clinical spectrum, and genotype-phenotype associations are beginning to be recognized. CONCLUSIONS AND RELEVANCEA high index of suspicion remains critical in diagnosing PCD.Children who have at least 2 of the major clinical features should be considered for further evaluation. Nevertheless, while newer tools have improved diagnostic capabilities, there is no single test that will diagnose every person with the disease. In people suspected of having PCD, nasal nitric oxide measurement is a useful screen, followed by diagnostic genetic testing and if negative, ciliary ultrastructural analysis. Despite otolaryngologic manifestations being common in infancy and persisting into adulthood, they have been understudied. Indeed, there are few randomized clinical trials examining the medicosurgical approaches to respiratory disease.

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The role of cilia for hydrocephalus formation

Wallmeier

Dallmayer

Omran

2022

American J of Med Genetics Pt C

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Hydrocephalus is a common finding in newborns. In most cases, it is caused by intraventricular hemorrhage associated with prematurity, whereas in some patients the cause of hydrocephalus can be traced back to genetic changes, associated with disease syndromes such as RASopathies, lysosomal storage diseases, dystroglycanopathies, craniosynostosis but also ciliopathies. Ciliopathies are a group of diseases that can affect multiple organ systems due to dysfunction or the absence of cilia. Cilia are small organelles, extending from the cell surface. Nonmotile monocilia are ubiquitously present during cell development fulfilling chemosensory functions, whereas specialized epithelia such as the ependyma, lining the inner surface of the brain ventricles, exhibit multiciliated cells propelling fluids along the cell surface. This review highlights ciliopathies and their pathophysiology in congenital hydrocephalus. While nonmotile ciliopathies are often associated with severe prenatal hydrocephalus combined with other severe congenital brain malformations, motile ciliopathies, especially those associated with defects in multiciliogenesis can cause hydrocephalus and chronic lung disease.

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MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia

Cited by 225 publications

References 18 publications

Diagnostic Methods in Primary Ciliary Dyskinesia

Diagnostic Methods in Primary Ciliary Dyskinesia

Advances in the Diagnosis and Treatment of Primary Ciliary Dyskinesia

The role of cilia for hydrocephalus formation

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