Longitudinal Lung Volume Changes by Ultrastructure and Genotype in Primary Ciliary Dyskinesia

Pifferi, Massimo; Bush, Andrew; Mulè, Giuseppe; Gracci, Serena; Fonnesu, Rossella; Michelucci, Angela; Cangiotti, Angela Maria; Caligo, Maria A.; Miccoli, Mario; Boner, Attilio; Peroni, Diego

doi:10.1513/annalsats.202007-816oc

Cited by 17 publications

(17 citation statements)

References 37 publications

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“…The most common cilia ultrastructure anomaly described is absence of the outer dynein arm. This finding is reported to occur in at least 20 of the ~50 published genes [ 92 ]. Structural proteins (DNAH5, DNAI1, DNAI2, NME8) [ 50 , 52 , 53 , 56 ], dynein arm docking complexes (CCDC114, CCDC151, ARMC4, TTC25) [ 57 , 59 , 61 , 62 ], and attachment factor CCDC103 [ 43 ] all routinely demonstrate absence of outer dynein arms.…”

Section: Genotype and Phenotype Associationsmentioning

confidence: 78%

“…Both gene products must be functional for normal cilia assembly, and a defect in one of these proteins cannot be compensated by a functional counterpart [ 80 , 91 ]. Notably, studies have shown that children who have biallelic mutations in CCDC39 or CCDC40 have nutritional deficits, greater lung disease, and more rapid pulmonary function decline when compared with individuals with other ultrastructural defects [ 80 , 91 , 92 ]. A brief report also suggested that both men and women who have these genetic and ultrastructural defects are more likely be infertile [ 21 ].…”

Section: Genotype and Phenotype Associationsmentioning

confidence: 99%

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Emerging Genotype-Phenotype Relationships in Primary Ciliary Dyskinesia

Brennan

Ferkol

Davis

2021

IJMS

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Primary ciliary dyskinesia (PCD) is a rare inherited condition affecting motile cilia and leading to organ laterality defects, recurrent sino-pulmonary infections, bronchiectasis, and severe lung disease. Research over the past twenty years has revealed variability in clinical presentations, ranging from mild to more severe phenotypes. Genotype and phenotype relationships have emerged. The increasing availability of genetic panels for PCD continue to redefine these genotype-phenotype relationships and reveal milder forms of disease that had previously gone unrecognized.

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Section: Genotype and Phenotype Associationsmentioning

confidence: 78%

Section: Genotype and Phenotype Associationsmentioning

confidence: 99%

Emerging Genotype-Phenotype Relationships in Primary Ciliary Dyskinesia

Brennan

Ferkol

Davis

2021

IJMS

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“…Several studies have systematically investigated associations between genotype and phenotype in PCD, which is a genetically heterogeneous disorder. It has been reported that lung function was signi cantly worse in individuals with CCDC39 and CCDC40 mutations and better in those with DNAH11 and DNAH5 mutations [17] . Consistent with the report of Shoemark et al, highly phenotypically diverse were also observed in our cohort [10] .…”

Section: Discussionmentioning

confidence: 99%

“…The relationship between genotype and phenotype in PCD has been considered a matter of critical importance [3] , as better understanding of genotypephenotype correlations helps to promote more accurate prognostic assessments. It has been reported that patients with a CCDC39 or CCDC40 mutation have lower body mass indices and worse lung function that declines more rapidly compared with those with DNAH5 mutations [4] . Conversely, patients with RSPH1 and DNAH9 mutations appear to have a milder respiratory phenotype [5,6] .…”

Section: Introductionmentioning

confidence: 99%

Considerable variability in the clinical and ciliary features of primary ciliary dyskinesia in patients with DNAH5 mutations

Guo

Chen

et al. 2022

Preprint

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Background: Primary ciliary dyskinesia (PCD) is a clinically and genetically heterogeneous disorder, but the relationship between genotype and phenotype is poorly established. We aimed to characterize the detailed clinical characteristics, ciliary phenotype and mutational spectrum of PCD patients with DNAH5 mutations.Methods: Whole exome sequencing followed by targeted copy number variation (CNV) analysis was used to screen 114 Chinese patients with highly suspected PCD. In cases with DNAH5 mutation, detailed demographic and clinical data, as well as ciliary beat pattern and ciliary ultrastructure, were comprehensively reviewed. Results: Thirty patients (median, 15.3 years; range, 0.6 to 43 years), who carried DNAH5 mutation, were identified. We characterized 38 novel and 7 known DNAH5 mutations (10 nonsense, 5 frameshift, 10 splicing, 16 missense mutations, 2 in-frame deletions and 2 large deletions). Despite bearing the same genotype, patients presented a highly variable phenotypic picture, including milder respiratory symptom, normal nasal nitric oxide levels (2/21, 9.5%) and “nontypical” ciliary beat pattern (4/21, 19.0%). Conclusions: DNAH5-associated PCD disease demonstrates dramatic phenotypic heterogeneity, contributing to the challenges of diagnosis. A composite work-up and cautious interpretation of the results are necessary during the PCD diagnosis process.

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“…PCD is a rare genetic multi-system disease where dysfunctional cilia lead to impaired mucociliary clearance, situs defects, congenital heart defects, and other health problems [12][13][14][15][16]. PCD is characterized by chronic upper and lower airway disease [13,[17][18][19][20], reduced lung function, and in some cases supplementary oxygen [21][22][23][24][25]. At the beginning of the pandemic, people with PCD and other chronic respiratory diseases were thought to be at high risk of severe COVID-19 disease.…”

Section: Introductionmentioning

confidence: 99%

COVID-19 Vaccinations: Perceptions and Behaviours in People with Primary Ciliary Dyskinesia

et al. 2021

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Primary ciliary dyskinesia (PCD) is a rare genetic disease that causes recurrent respiratory infections. People with PCD may be at higher risk of severe coronavirus disease 2019 (COVID-19), and therefore vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important. We studied vaccination willingness, speed of vaccination uptake, side effects, and changes in social contact behaviour after vaccination in people with PCD. We used data from COVID-PCD, an international participatory cohort study. A COVID-19 vaccination questionnaire was emailed to participants in May 2021 and 423 participants from 31 countries replied (median age: 30 years, range 1–85 years; 261 (62%) female). Vaccination uptake and willingness were high, with 273 of 287 adults (96%) being vaccinated or willing to be in June 2021; only 4% were hesitant. The most common reason for hesitancy was fear of side effects, reported by 88%. Mild side effects were common, but no participant reported severe side effects. Half of the participants changed their social behaviour after vaccination by seeing friends and family more often. The high vaccination willingness in the study population might reflect the extraordinary effort taken by PCD support groups to inform people about COVID-19 vaccination. Clear and specific information and involvement of representatives is important for high vaccine uptake.

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Longitudinal Lung Volume Changes by Ultrastructure and Genotype in Primary Ciliary Dyskinesia

Cited by 17 publications

References 37 publications

Emerging Genotype-Phenotype Relationships in Primary Ciliary Dyskinesia

Emerging Genotype-Phenotype Relationships in Primary Ciliary Dyskinesia

Considerable variability in the clinical and ciliary features of primary ciliary dyskinesia in patients with DNAH5 mutations

COVID-19 Vaccinations: Perceptions and Behaviours in People with Primary Ciliary Dyskinesia

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