The global prevalence and ethnic heterogeneity of primary ciliary dyskinesia gene variants: a genetic database analysis

Hannah, William B.; Seifert, Bryce A.; Truty, Rebecca; Zariwala, Maimoona A.; Ameel, Kristen; Zhao, Yi; Nykamp, Keith; Gaston, Benjamin

doi:10.1016/s2213-2600(21)00453-7

Cited by 117 publications

(88 citation statements)

References 41 publications

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“…The frequency of asthenozoospermia related to dynein deficiencies in the general population has not been determined, whereas one in every 7554 people carries a pathogenic variant for PCD. 66 Given the fact that nearly 80% of the semen samples of infertile men show impaired sperm motility, 67 it would be interesting to do a large-scale population study on the incidence of dynein variants among these men. This highlights the importance of providing genetic counseling to couples who have reported dynein gene variants in order to prevent fertility concerns from being passed down to future generations.…”

Section: Discussionmentioning

confidence: 99%

Potential role of dynein‐related genes in the etiology of male infertility: A systematic review and a meta‐analysis

2022

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Background The dynein‐related genes may have a role in the etiology of male infertility, particularly in cases of impaired sperm motility. Objectives The goal of this review is to compile a list of the most important dynein‐related candidate genes that may contribute to male factor infertility. Materials and methods Databases were searched using the keywords “dynein,” “male,” “infertility,” and by applying strict inclusion criteria. A meta‐analysis was also performed by using the eligible case‐control studies. The odd ratios (ORs), the Z‐test score, and the level of significance were determined using a fixed model with a p value of 0.05. Funnel plots were used to check for publication bias. Results There were 35 studies that met the inclusion criteria. There were a total of 15 genes responsible for the production of dynein structural proteins, the production of dynein assembling factors, and potentially associated with male infertility. A total of five case‐control studies were eligible for inclusion in the meta‐analysis. Variants in the dynein‐related genes were linked to an increased the risk of male infertility (OR = 21.52, 95% confidence interval 8.34–55.50, Z test = 6.35, p < 0.05). The percentage of heterogeneity, I2, was 47.00%. The lack of variants in the dynein genes was an advantage, and this was statistically significant. Discussion The results from the present review illustrate that pathogenic variants in genes both for dynein synthesis and for dynein assembly factors could be associated with isolated cases of male infertility without any other symptoms. Conclusions The genes addressed in this study, which are involved in both the production and assembly of dynein, could be used as molecular targets for future research into the etiology of sperm motility problems.

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Section: Discussionmentioning

confidence: 99%

Potential role of dynein‐related genes in the etiology of male infertility: A systematic review and a meta‐analysis

2022

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“…PCD probably occurs in all ethnic groups around the globe but is best described in the western parts of the world, mainly due to the required significantly resource‐intensive diagnostics (Lucas et al, 2017; Shapiro et al, 2016). Traditionally, global prevalence is stated to be probably at least 1:10,000 (Wallmeier et al, 2020), but a new publication describes a general incidence of 1 out of 7.7554 people with surprisingly frequent incidence in people of African descent (Hannah et al, 2022). Such prevalence would mean that there are approximately 45,000 people with PCD among EU citizens alone.…”

Section: Primary Ciliary Dyskinesia—a Chronic Respiratory Motile Cili...mentioning

confidence: 99%

Chronic airway disease in primary ciliary dyskinesia—spiced with geno–phenotype associations

Nielsen

Holgersen

Crowley

et al. 2022

American J of Med Genetics Pt C

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Primary ciliary dyskinesia (PCD) can be defined as a multiorgan ciliopathy with a dominant element of chronic airway disease affecting the nose, sinuses, middle ear, and in particular, the lower airways. Although most patients with PCD are diagnosed during preschool years, it is obvious that the chronic lung disease starts its course already from birth. The many faces of the clinical picture change, as does lung function, structural lung damage, the burden of infection, and of treatment throughout life. A markedly severe neutrophil inflammation in the respiratory tract seems pervasive and is only to a minimal extent ameliorated by a treatment strategy, which is predominantly aimed at bacterial infections. An ever-increasing understanding of the different aspects, their interrelationships, and possible different age courses conditioned by the underlying genotype is the focus of much attention. The future is likely to offer personalized medicine in the form of mRNA therapy, but to that end, it is of utmost importance that all patients with PCD be carefully characterized and given a genetic diagnosis. In this narrative review, we have concentrated on lower airways and summarized the current understanding of the chronic airway disease in this motile ciliopathy. In addition, we highlight the challenges, gaps, and opportunities in PCD lung disease research.

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“…With increasing knowledge about the genetic background of PCD, the genotype–phenotype correlations are becoming more apparent. Given the rare nature of PCD, with an estimated prevalence of at least 1:7,500 (Hannah et al, 2022), most knowledge on genotype–phenotype correlations has been derived from small case series. Mutations in multiciliogenesis genes, like CCNO and MCIDAS , have been associated with poor clinical outcome.…”

Section: Introductionmentioning

confidence: 99%

Primary ciliary dyskinesia in Volendam: Diagnostic and phenotypic features in patients with a CCDC114 mutation

Israëls

Gogh

et al. 2022

American J of Med Genetics Pt C

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Primary ciliary dyskinesia (PCD) is a heterogeneous disease, with impaired mucociliary clearance causing respiratory tract infections. A founding CCDC114 mutation has led to a relatively homogeneous and large Dutch PCD population in Volendam. Our aim was to describe their phenotype. Therefore, all Volendam PCD patients seen at the Amsterdam UMC were included in this study. Data were collected on lung function, microbiology, radiology, and ear-nose-throat (ENT) symptoms. A mixed effects model estimated lung function decline in %point per year (95% confidence interval [CI]). Thirty-three (60%) out of approximately 56 Volendam PCD patients were treated at our center and included in this study. Only 30% of patients had situs inversus. FEV 1 declined in children (À1.43%/year, CI: À1.80/À1.05), but not in adults (0.01%/year, CI: À0.36/0.38). Pseudomonas aeruginosa was cultured in 21% of children and 60% of adults, respectively. Patients who have been infected at some point with P. aeruginosa had a steeper decline in FEV 1 as compared to patients that have never been infected. Neonatal symptoms (79%) and ENT problems (94%) were common; fertility issues however, were not (11%) common. Compared to other PCD cohorts, the Volendam/CCDC114 patients have a moderately severe phenotype with lung function decline predominantly occurring in childhood.

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The global prevalence and ethnic heterogeneity of primary ciliary dyskinesia gene variants: a genetic database analysis

Cited by 117 publications

References 41 publications

Potential role of dynein‐related genes in the etiology of male infertility: A systematic review and a meta‐analysis

Potential role of dynein‐related genes in the etiology of male infertility: A systematic review and a meta‐analysis

Chronic airway disease in primary ciliary dyskinesia—spiced with geno–phenotype associations

Primary ciliary dyskinesia in Volendam: Diagnostic and phenotypic features in patients with a CCDC114 mutation

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