Primary ciliary dyskinesia due to DRC1/CCDC164 gene mutation

Benjamin, Antony Terance; Ganesh, Ram; Chinnappa, Jagdish; Kinimi, Ilin; Lucas, Jane S.

doi:10.4103/lungindia.lungindia_361_19

Cited by 9 publications

(6 citation statements)

References 6 publications

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“…In those three independent studies, the ciliary ultrastructural findings were heterogeneous, with predominance of axonemal microtubular disorganization. In India, a homozygous nonsense DRC1 variant, resulting in a stop codon occurring in exon 10, was also observed (NM_145038: c.1205G>A; p.Trp402*) [ 59 ]. In this study, TEM was not performed; thus, we could not compare the findings, but HSVM analysis also revealed dyskinetic movement in most cilia [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

“…In India, a homozygous nonsense DRC1 variant, resulting in a stop codon occurring in exon 10, was also observed (NM_145038: c.1205G>A; p.Trp402*) [ 59 ]. In this study, TEM was not performed; thus, we could not compare the findings, but HSVM analysis also revealed dyskinetic movement in most cilia [ 59 ]. In Tunisia, a frameshift DRC1 variant was observed in exon 2 (c.2012_213del; p. Ser70Argfs*11).…”

Section: Discussionmentioning

confidence: 99%

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Characterization of a DRC1 null variant associated with primary ciliary dyskinesia and female infertility

Pereira

Carvalho

Dias

et al. 2023

J Assist Reprod Genet

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Propose We here present a female case with primary ciliary dyskinesia (PCD) and infertility. In this report, we also present the evaluation of the patient family, including her twin sister, also with PCD and infertility. Methods Confirmation of the PCD clinical diagnosis was performed through assessment of cilia motility, by high-speed video microscopy (HSVM), axoneme ultrastructure, by transmission electron microscopy (TEM), and genetic characterization, by whole-exome sequence (WES). Gene expression studies used qPCR for mRNA expression and immunofluorescence to determine cell protein localization. Results We identified a homozygous nonsense variant in the DRC1 gene (NM 145038.5:c.352C>T (p.Gln118Ter)) in the female patient with PCD and infertility that fit the model of autosomal recessive genetic transmission. This variant eventually results in a dyskinetic ciliary beat with a lower frequency and a partial lack of both dynein arms as revealed by TEM analysis. Moreover, this variant implies a decrease in the expression of DRC1 mRNA and protein. Additionally, expression analysis suggested that DRC1 may interact with other DRC elements. Conclusions Our findings suggest that the DRC1 null variant leads to PCD associated with infertility, likely caused by defects in axoneme from Fallopian tube cilia. Overall, our outcomes contribute to a better understanding of the genetic factors involved in the pathophysiology of PCD and infertility, and they highlight the interaction of different genes in the patient phenotype, which should be investigated further because it may explain the high heterogeneity observed in PCD patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Characterization of a DRC1 null variant associated with primary ciliary dyskinesia and female infertility

Pereira

Carvalho

Dias

et al. 2023

J Assist Reprod Genet

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“…Previous studies from Japan showed that variation (large homozygous deletion) in DRC1 plays an important role in primary ciliary dyskinesia (PCD), a rare genetic disorder that prevents the clearance of mucous from the lungs, leading to frequent respiratory infections caused by bacteria and other irritants in the mucous [ 20 , 21 , 22 ]. Moreover, the DRC1 / CCDC164 mutation significant in PCD was identified in India [ 23 ]. To the best of our knowledge, our study is the first to describe the association between the variation in DRC1 and COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Gene Variants Related to Cardiovascular and Pulmonary Diseases May Correlate with Severe Outcome of COVID-19

Sypniewski

Król

Szyda

et al. 2022

IJMS

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Background: Severe outcomes of COVID-19 account for up to 15% of all cases. The study aims to check if any gene variants related to cardiovascular (CVD) and pulmonary diseases (PD) are correlated with a severe outcome of COVID-19 in a Polish cohort of COVID-19 patients. Methods: In this study, a subset of 747 samples from unrelated individuals collected across Poland in 2020 and 2021 was used and whole-genome sequencing was performed. Results: The GWAS analysis of SNPs and short indels located in genes related to CVD identified one variant significant in COVID-19 severe outcome in the HADHA gene, while for the PD gene panel, we found two significant variants in the DRC1 gene. In this study, both potentially protective and risk variants were identified, of which variants in the HADHA gene deserve the most attention. Conclusions: This is the first study reporting the association between the HADHA and DRC1 genetic variants and COVID-19 severe outcome based on the cohort WGS analysis. Although all the identified variants are localised in introns, they may be correlated and therefore inherited along with other risk variants, potentially causative to severe outcome of COVID-19 but not discovered yet.

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“…Two other works with Asian patients, also found a DRC1 large deletion (c.1-3952_540+1331del) . In India, a homozygous nonsense DRC1 variant, resulting in a stop codon occurring in exon 10, was also observed (NM_145038: c.1205G>A; p.Trp402*) [53]. In Tunisia, a frameshift DRC1 variant was observed in exon 2 (c.2012_213del; p. Ser70Argfs*11) [54].…”

Section: Discussionmentioning

confidence: 99%

Characterization of a DRC1 null variant associated to primary ciliary dyskinesia and female infertility

Pereira

Carvalho

Dias

et al. 2022

Preprint

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Background: Primary ciliary dyskinesia (PCD; MIM #242650) is a rare multisystemic genetic diseases, whose diagnostic is challenge. Additional data to complete the complex puzzle of PCD genomic analysis is of upmost importance to better understand PCD pathophysiology. We here present a female case with PCD and infertility. We also present the evaluation of the patient family, including her twin sister, also with PCD and infertility.Methods: Confirmation of the PCD clinical diagnosis was performed through assessment of cilia motility, by high-speed video microscopy (HSVM), axoneme ultrastructure, by transmission electron microscopy (TEM), and genetic characterization, by whole exome sequence (WES). Gene expression studies used qPCR for mRNA expression and immunofluorescence to determine cell protein localization.Results: HSVM analysis revealed that the ciliary beat frequency was decreased, with mostly cilia presenting dyskinetic movements. TEM analysis showed partial absence of both dynein arms associated with high ciliary deviation. WES analysis evidenced a homozygous nonsense variant in the DRC1 gene, belonging to the dynein regulatory complex (DRC). Expression of DRC1 mRNA and protein were decreased. Expression analysis of the DRC1 mRNA also evidenced an interaction with other DRC components. Family analysis revealed the same homozygous variant in the twin sister and, in heterozygosity in parents and daughters. Both the patient and her twin sister presented idiopathic infertility.Conclusions: Overall, our results contribute to increase understanding of the genetic factors involved in the pathophysiology of PCD and infertility, and highlight the interaction of different genes in the patient phenotype, which should be further explored, as it may justify the highly heterogeneity observed in PCD patients. Understanding the genetic etiology of PCD is of paramount importance to assist the diagnosis and development of newer therapies.

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Primary ciliary dyskinesia due to DRC1/CCDC164 gene mutation

Cited by 9 publications

References 6 publications

Characterization of a DRC1 null variant associated with primary ciliary dyskinesia and female infertility

Characterization of a DRC1 null variant associated with primary ciliary dyskinesia and female infertility

Gene Variants Related to Cardiovascular and Pulmonary Diseases May Correlate with Severe Outcome of COVID-19

Characterization of a DRC1 null variant associated to primary ciliary dyskinesia and female infertility

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