Risk factors for situs defects and congenital heart disease in primary ciliary dyskinesia

Best, Sunayna; Shoemark, Amelia; Rubbo, Bruna; Patel, Mitali; Fassad, Mahmoud R; Dixon, Mellisa; Rogers, Andrew V.; Hirst, Robert A.; Rutman, Andrew; Ollosson, Sarah; Jackson, Claire; Goggin, Patricia; Thomas, Simon; Pengelly, Reuben J.; Cullup, Thomas; Pissaridou, Eleni; Hayward, Jane; Onoufriadis, Alexandros; O’Callaghan, Christopher; Loebinger, Michael R.; Wilson, Robert; Chung, Eddie M.K.; Kenia, Priti; Doughty, Victoria L; Carvalho, J. S.; Lucas, Jane S.; Mitchison, Hannah M.; Hogg, Claire

doi:10.1136/thoraxjnl-2018-212104

Cited by 62 publications

(69 citation statements)

References 10 publications

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“…The distribution of cardiac situs according to the mutated PCD genes showed that patients with mutations in PCD genes can have either normal or abnormal cardiac situs. As expected, only normal cardiac situs (levocardia) was reported in patients with mutations in a specific subset of PCD genes including genes encoding central complex components ( HYDIN ), radial spokes components ( RSPH9 , RSPH4A , DNAJB13 ) and genes essential for multiciliogenesis ( CCNO ) (Figure A,B).…”

Section: Resultssupporting

confidence: 85%

“…Affected individuals present with a range of nonspecific manifestations including chronic wet cough, rhinosinusitis, otitis media and hearing impairment. About 50% of patients have laterality problems . Infertility is frequently present in affected adult males …”

Section: Introductionmentioning

confidence: 99%

“…About 50% of patients have laterality problems. 1 Infertility is frequently present in affected adult males. 2 PCD is primarily an autosomal and X-linked recessive disease.…”

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confidence: 99%

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Clinical and genetic spectrum in 33 Egyptian families with suspected primary ciliary dyskinesia

et al. 2019

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Primary ciliary dyskinesia (PCD) is a rare genetic disorder of motile cilia dysfunction generally inherited as an autosomal recessive disease. Genetic testing is increasingly considered an early step in the PCD diagnostic workflow. We used targeted panel next‐generation sequencing (NGS) for genetic screening of 33 Egyptian families with clinically highly suspected PCD. All variants prioritized were Sanger confirmed in the affected individuals and correctly segregated within the family. Targeted NGS yielded a high diagnostic output (70%) with biallelic mutations identified in known PCD genes. Mutations were identified in 13 genes overall, with CCDC40 and CCDC39 the most frequently mutated genes among Egyptian patients. Most identified mutations were predicted null effect variants (79%) and not reported before (85%). This study reveals that the genetic landscape of PCD among Egyptians is highly heterogeneous, indicating that a targeted NGS approach covering multiple genes will provide a superior diagnostic yield compared to Sanger sequencing for genetic diagnosis. The high diagnostic output achieved here highlights the potential of placing genetic testing early within the diagnostic workflow for PCD, in particular in developing countries where other diagnostic tests can be less available.

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Section: Resultssupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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Clinical and genetic spectrum in 33 Egyptian families with suspected primary ciliary dyskinesia

et al. 2019

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“…The first link between cilia and LR asymmetry was inspired by the observation that patients with PCD often have SIT (Sutherland & Ware, 2009). Three past studies investigated the accurate rates of laterality defects in PCD, with combined results showing 41.0%-47.7% of patients with PCD had SIT (Best et al, 2019;Shapiro, Davis, & Ferkol, 2014;Shapiro et al, 2007). On the other hand, careful screening for PCD in SIT cases is still necessary.…”

Section: Discussionmentioning

confidence: 99%

“…We classified cases as situs ambiguous if any of the abnormalities was detected, such as mesocardia or isolated dextrocardia, absent/interrupted inferior vena cava, atrial isomerism or atrial situs ambiguous, bronchial isomerism or pulmonary isomerism, thoracic SI, polysplenia or asplenia, midline liver, abdominal SI and (2) SIT, defined as complete mirror‐imaged arrangement of thoracic and abdominal organs. The diagnosis of SIT refered to the study by Best et al () and Kennedy et al (). If the stomach and heart were on the right, liver on the left, the patients were assumed to have SIT, unless detailed imaging reports to suggest situs ambiguous.…”

Section: Methodsmentioning

confidence: 99%

Comorbidities in situs inversus totalis: A hospital‐based study

Chen

Guo

Qian

et al. 2020

Birth Defects Research

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Background and objective Few studies have assessed the comorbid diseases in situs inversus totalis (SIT) comprehensively. The aim of this study was to provide insight into the spectrum and prevalence of comorbidities in SIT. Methods Children ≤18 years of age with SIT were enrolled in this retrospective observational study. Situs status and comorbidities were independently confirmed by two physicians, based on review of radiologic, ultrasonic examination, operative records, and case notes. Results A total of 155 children (median age: 1.24 years; range: 1 day–17.8 years) confirmed to have SIT were recruited between January 2008 and December 2018. Associated conditions were diagnosed in 114 children (73.5%). Among them, 25 children (16.1%) had multiple anomalies affecting two or more organ systems. The most commonly associated conditions were congenital heart defects (n = 72, 46.5%) followed by primary ciliary dyskinesia (n = 19, 12.3%), renal disorders (n = 12, 7.7%), biliary atresia (n = 7, 4.5%), skeletal dysplasia (n = 8, 5.2%), and mental retardation (n = 4, 2.6%). Conclusion A substantial proportion of children with SIT have comorbidities affecting multiple systems, especially cardiovascular and respiratory abnormalities. Children with SIT warrant careful examination for the presence of congenital and acquired abnormalities.

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Structures and functions of cilia during vertebrate embryo development

Amack

2022

Molecular Reproduction Devel

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Cilia are hair‐like structures that project from the surface of cells. In vertebrates, most cells have an immotile primary cilium that mediates cell signaling, and some specialized cells assemble one or multiple cilia that are motile and beat synchronously to move fluids in one direction. Gene mutations that alter cilia structure or function cause a broad spectrum of disorders termed ciliopathies that impact virtually every system in the body. A wide range of birth defects associated with ciliopathies underscores critical functions for cilia during embryonic development. In many cases, the mechanisms underlying cilia functions during development and disease remain poorly understood. This review describes different types of cilia in vertebrate embryos and discusses recent research results from diverse model systems that provide novel insights into how cilia form and function during embryo development. The work discussed here not only expands our understanding of in vivo cilia biology, but also opens new questions about cilia and their roles in establishing healthy embryos.

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Risk factors for situs defects and congenital heart disease in primary ciliary dyskinesia

Cited by 62 publications

References 10 publications

Clinical and genetic spectrum in 33 Egyptian families with suspected primary ciliary dyskinesia

Clinical and genetic spectrum in 33 Egyptian families with suspected primary ciliary dyskinesia

Comorbidities in situs inversus totalis: A hospital‐based study

Structures and functions of cilia during vertebrate embryo development

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