scholarly journals What do we know about the genetic background of primary ciliary dyskinesia (PCD) and the reproductive approach?

2019 ◽  
Vol 2 (2) ◽  
pp. 57-62
Author(s):  
Sanja Vujisic
Keyword(s):  
Genetic Testing ◽  
Genetic Background ◽  
Primary Ciliary Dyskinesia ◽  
Semen Analysis ◽  
Genetic Disorder ◽  
Blood Draw ◽  
Preparation Methods ◽  
Strict Adherence ◽  
Gradient Density ◽  
Ciliary Dyskinesia

Introduction: Primary ciliary dyskinesia (PCD; MIM 244400) is a heterogeneous autosomal recessive genetic disorder associated with infertility due to impaired sperm motility in men. We describe two such cases and give a literature review on the genetic background and reproductive outcome. Materials and methods: Two primary infertile couples were referred to our clinic. Native semen, analyzed according to the WHO manual (2010), showed that male partners have completely immotile sperm with a negative pentoxifylline test. Sample vitality was compared according to different semen preparation methods (gradient density and washing method only). Genetic testing was done by Whole Exome next-generation Sequencing (WES) analysis. For the IVF/ICSI procedure, semen was prepared using the gradient density method, and prior to the ICSI procedure itself, a hypo-osmotic swelling test (HOST) was done. Results: Semen analysis showed oligoasthenozoospermia in Patient 1 and oligoasthenoteratozoospermia in Patient 2. Blood draw for hormones and karyotype showed no irregularities in either case. Patient 1 was previously diagnosed with PCD, while Patient 2 was not. Parallel vitality testing did not show any differences between the two semen preparation methods in either of the two cases. Genetic testing in Patient 2 showed a pathogenic apparently homozygous CCDC40:c.2440C>T variant in exon 14 of the CCDC40 gene (MIM 613799). Fertilization rate after HOST/ICSI in both patients was 100%, and the final outcome for both patients was the birth of a healthy child. Conclusion: Although PCD has diverse etiology, assisted reproduction techniques such as HOST give these couples a good chance for parenthood. Advances in testing and strict adherence to advised procedures are to be credited for such outcome improvement. Additionally, our recommendation for PCD patients and patients with immotile sperm is to do genetic testing and counselling prior to the IVF/ICSI procedure.

scholarly journals Progress in Diagnosing Primary Ciliary Dyskinesia: The North American Perspective

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1278
Author(s):  
Michael Glenn O’Connor ◽  
Amjad Horani ◽  
Adam J. Shapiro
Keyword(s):  
Genetic Testing ◽  
North America ◽  
North American ◽  
Primary Ciliary Dyskinesia ◽  
Clinical Phenotype ◽  
The United States ◽  
Diagnostic Process ◽  
The North ◽  
Diagnostic Guideline ◽  
Ciliary Dyskinesia

Primary Ciliary Dyskinesia (PCD) is a rare, under-recognized disease that affects respiratory ciliary function, resulting in chronic oto-sino-pulmonary disease. The PCD clinical phenotype overlaps with other common respiratory conditions and no single diagnostic test detects all forms of PCD. In 2018, PCD experts collaborated with the American Thoracic Society (ATS) to create a clinical diagnostic guideline for patients across North America, specifically considering the local resources and limitations for PCD diagnosis in the United States and Canada. Nasal nitric oxide (nNO) testing is recommended for first-line testing in patients ≥5 years old with a compatible clinical phenotype; however, all low nNO values require confirmation with genetic testing or ciliary electron micrograph (EM) analysis. Furthermore, these guidelines recognize that not all North American patients have access to nNO testing and isolated genetic testing is appropriate in cases with strong clinical PCD phenotypes. For unresolved diagnostic cases, referral to a PCD Foundation accredited center is recommended. The purpose of this narrative review is to provide insight on the North American PCD diagnostic process, to enhance the understanding of and adherence to current guidelines, and to promote collaboration with diagnostic pathways used outside of North America.

scholarly journals Deep phenotyping, including quantitative ciliary beating parameters, and extensive genotyping in primary ciliary dyskinesia

2019 ◽  
Vol 57 (4) ◽  
pp. 237-244 ◽  
Author(s):  
Sylvain Blanchon ◽  
Marie Legendre ◽  
Mathieu Bottier ◽  
Aline Tamalet ◽  
Guy Montantin ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Genetic Disorder ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Central Complex ◽  
Ciliary Beating ◽  
Recovery Stroke ◽  
Biallelic Mutations ◽  
Ciliary Dyskinesia

BackgroundPrimary ciliary dyskinesia (PCD) is a rare genetic disorder resulting in abnormal ciliary motility/structure, extremely heterogeneous at genetic and ultrastructural levels. We aimed, in light of extensive genotyping, to identify specific and quantitative ciliary beating anomalies, according to the ultrastructural phenotype.MethodsWe prospectively included 75 patients with PCD exhibiting the main five ultrastructural phenotypes (n=15/group), screened all corresponding PCD genes and measured quantitative beating parameters by high-speed video-microscopy (HSV).ResultsSixty-eight (91%) patients carried biallelic mutations. Combined outer/inner dynein arms (ODA/IDA) defect induces total ciliary immotility, regardless of the gene involved. ODA defect induces a residual beating with dramatically low ciliary beat frequency (CBF) related to increased recovery stroke and pause durations, especially in case of DNAI1 mutations. IDA defect with microtubular disorganisation induces a low percentage of beating cilia with decreased beating angle and, in case of CCDC39 mutations, a relatively conserved mean CBF with a high maximal CBF. Central complex defect induces nearly normal beating parameters, regardless of the gene involved, and a gyrating motion in a minority of ciliated edges, especially in case of RSPH1 mutations. PCD with normal ultrastructure exhibits heterogeneous HSV values, but mostly an increased CBF with an extremely high maximal CBF.ConclusionQuantitative HSV analysis in PCD objectives beating anomalies associated with specific ciliary ultrastructures and genotypes. It represents a promising approach to guide the molecular analyses towards the best candidate gene(s) to be analysed or to assess the pathogenicity of the numerous sequence variants identified by next-generation-sequencing.

scholarly journals Diagnosis of primary ciliary dyskinesia

2015 ◽  
Vol 41 (3) ◽  
pp. 251-263 ◽  
Author(s):  
Mary Anne Kowal Olm ◽  
Elia Garcia Caldini ◽  
Thais Mauad
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Bacterial Colonization ◽  
Genetic Disorder ◽  
Signs And Symptoms ◽  
Screening Tests ◽  
Lower Airway ◽  
Airway Infections ◽  
Means Of Transmission ◽  
Respiratory Signs And Symptoms ◽  
Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a genetic disorder of ciliary structure or function. It results in mucus accumulation and bacterial colonization of the respiratory tract which leads to chronic upper and lower airway infections, organ laterality defects, and fertility problems. We review the respiratory signs and symptoms of PCD, as well as the screening tests for and diagnostic investigation of the disease, together with details related to ciliary function, ciliary ultrastructure, and genetic studies. In addition, we describe the difficulties in diagnosing PCD by means of transmission electron microscopy, as well as describing patient follow-up procedures.

scholarly journals Clinical characteristics and genetic spectrum of 26 individuals of Chinese origin with primary ciliary dyskinesia

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xinyue Zhao ◽  
Chun Bian ◽  
Keqiang Liu ◽  
Wenshuai Xu ◽  
Yaping Liu ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Clinical Characteristics ◽  
Genetic Disorder ◽  
Copy Number Variations ◽  
Pathogenic Mutations ◽  
Chinese Origin ◽  
Whole Exome ◽  
Low Pass ◽  
Ciliary Dyskinesia

Abstract Background Primary ciliary dyskinesia (PCD) is a rare, highly heterogeneous genetic disorder involving the impairment of motile cilia. With no single gold standard for PCD diagnosis and complicated multiorgan dysfunction, the diagnosis of PCD can be difficult in clinical settings. Some methods for diagnosis, such as nasal nitric oxide measurement and digital high-speed video microscopy with ciliary beat pattern analysis, can be expensive or unavailable. To confirm PCD diagnosis, we used a strategy combining assessment of typical symptoms with whole-exome sequencing (WES) and/or low-pass whole-genome sequencing (WGS) as an unbiased detection tool to identify known pathogenic mutations, novel variations, and copy number variations. Results A total of 26 individuals of Chinese origin with a confirmed PCD diagnosis aged 13 to 61 years (median age, 24.5 years) were included. Biallelic pathogenic mutations were identified in 19 of the 26 patients, including 8 recorded HGMD mutations and 24 novel mutations. The detection rate reached 73.1%. DNAH5 was the most frequently mutated gene, and c.8383C > T was the most common mutated variant, but it is relatively rare in PCD patients from other ethnic groups. Conclusion This study demonstrates the practical clinical utility of combining WES and low-pass WGS as a no-bias detecting tool in adult patients with PCD, showing a clinical characteristics and genetic spectrum of Chinese PCD patients.

Rhinosinusitis in Pediatric Primary Ciliary Dyskinesia: Impact of Disease

2019 ◽  
Vol 161 (5) ◽  
pp. 877-880 ◽  
Author(s):  
Jay M. Bhatt ◽  
Ethan G. Muhonen ◽  
Maxene Meier ◽  
Scott D. Sagel ◽  
Kenny H. Chan
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Genetic Disorder ◽  
Retrospective Chart Review ◽  
Sinus Surgery ◽  
Record System ◽  
Sinus Disease ◽  
Respiratory Cilia ◽  
Genetic Test Results ◽  
Biallelic Mutations ◽  
Ciliary Dyskinesia

Objectives Primary ciliary dyskinesia (PCD) is a genetic disorder characterized by abnormal respiratory cilia ultrastructure and/or function causing defective mucociliary clearance. We investigated the extent and severity of rhinosinusitis in a large cohort of children with PCD and explored associations among risk factors, including genotype and sinus disease. Study Design Retrospective chart review. Setting Tertiary academic children’s hospital. Subjects and Methods A review was conducted with a patient registry at the PCD Foundation Center at our institution. Demographic, imaging, clinical, and operative data were reviewed through the institutional electronic health record system. Results Fifty-four subjects were identified with mean and median age at diagnosis of 5.2 and 4.0 years. The male:female ratio was 35%:65%. Sinus symptoms were present in 46 (85%) subjects, 22 of whom had chronic rhinosinusitis. Nineteen (35%) subjects underwent operative intervention, consisting of endoscopic sinus surgery (ESS; 16 patients) and maxillary lavage (3 patients). Nineteen subjects underwent adenoidectomy for PCD-related indications. Five sinus-related admissions in 3 subjects were noted during the study period, and no complication of rhinosinusitis occurred in the cohort. Genetic test results were available in 27 subjects, in whom 23 (85%) had biallelic mutations in a PCD gene. Demographic factors, Lund-Mackay score, and PCD genotype were not found to be predictors for ESS or hospitalization in our cohort. Conclusion While rhinosinusitis was common in our PCD cohort, most patients did not require ESS. Since complications of rhinosinusitis were uncommon, we recommend judicious surgical management tailored to the patient’s symptoms.

scholarly journals Ciliary beat pattern and frequency in genetic variants of primary ciliary dyskinesia

2014 ◽  
Vol 44 (6) ◽  
pp. 1579-1588 ◽  
Author(s):  
Johanna Raidt ◽  
Julia Wallmeier ◽  
Rim Hjeij ◽  
Jörg Große Onnebrink ◽  
Petra Pennekamp ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Genetic Disorder ◽  
Beat Frequency ◽  
Detailed Knowledge ◽  
Beat Pattern ◽  
Biallelic Mutations ◽  
Tract Infections ◽  
Ciliary Dyskinesia ◽  
Ciliary Beat

Primary ciliary dyskinesia (PCD) is a rare genetic disorder leading to recurrent respiratory tract infections. High-speed video-microscopy analysis (HVMA) of ciliary beating, currently the first-line diagnostic tool for PCD in most centres, is challenging because recent studies have expanded the spectrum of HVMA findings in PCD from grossly abnormal to very subtle. The objective of this study was to describe the diversity of HVMA findings in genetically confirmed PCD individuals.HVMA was performed as part of the routine work-up of individuals with suspected PCD. Subsequent molecular analysis identified biallelic mutations in the PCD-related genes of 66 individuals. 1072 videos of these subjects were assessed for correlation with the genotype.Biallelic mutations (19 novel) were found in 17 genes: DNAI1, DNAI2, DNAH5, DNAH11, CCDC103, ARMC4, KTU/DNAAF2, LRRC50/DNAAF1, LRRC6, DYX1C1, ZMYND10, CCDC39, CCDC40, CCDC164, HYDIN, RSPH4A and RSPH1. Ciliary beat pattern variations correlated well with the genetic findings, allowing the classification of typical HVMA findings for different genetic groups. In contrast, analysis of ciliary beat frequency did not result in additional diagnostic impact.In conclusion, this study provides detailed knowledge about the diversity of HVMA findings in PCD and may therefore be seen as a guide to the improvement of PCD diagnostics.

scholarly journals Investigation of Primary Ciliary Dyskinesia in Children with Bronchiectasis in Iran

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
sohila alyasin ◽  
Behjat Maneshian ◽  
Shadi Niliyeh
Keyword(s):  
Nitric Oxide ◽  
Situs Inversus ◽  
Primary Ciliary Dyskinesia ◽  
Genetic Disorder ◽  
Screening Tests ◽  
P Value ◽  
Genetic Studies ◽  
Rare Genetic Disorder ◽  
Exhaled No ◽  
Ciliary Dyskinesia

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder with signs and symptoms of recurrent chronic sinusitis, otitis media, pneumonia, bronchiectasis, male infertility, and situs inversus. The diagnosis of PCD has always been one of the more challenging issues that is mostly made through screening tests. These include the saccharin test and measurements of exhaled and nasal nitric oxide (NO) level, transmission electron microscopy (TEM) for evaluating ultrastructure of the cilia, high-speed video microscopy for evaluating ciliary beat patterns, immunofluorescent staining of the cilia in the biopsies, and genetic studies. As there had not been any epidemiological studies in Iran to detect the prevalence of PCD in the general population, the current research has been undertaken for the first time using screening tests of saccharin and measurement of the level of exhaled NO (fractional exhaled NO) to investigate the prevalence of PCD. Objectives: Primary ciliary dyskinesia (PCD) is a rare genetic disorder with the basis of an abnormal ciliary movement that causes chronic respiratory infections, bronchiectasis, infertility in males, and situs inversus. The significance of earlier diagnosis is for better care and prevention of complications. In this regard, we studied the PCD in children with bronchiectasis by saccharin test and measurement of exhaled nitric oxide. Methods: In this cross-sectional study, 31 patients with a definite diagnosis of bronchiectasis were evaluated regarding nitric oxide exhalatory measurement (FeNO) and a saccharin test for the confirmation of PCD diagnosis. The cut-off point of 20 ppb was considered as the normal level for FeNO test and the sensation of fewer than 60 minutes for the normal range of the saccharin test. Age, gender, and cardioposition were recorded for the patients. Results: Unlike the saccharine test, the measurement of exhaled nitric oxide had a high sensitivity (90.3% versus 54.8%) for the diagnosis of PCD. Cardioposition and gender did not have significant effects on the outcomes of exhaled NO and saccharin test (P-value > 0.05). Besides, the patients’ age did not affect FeNO measurement but was significantly higher among those with abnormal saccharin test (P-value = 0.028). Conclusions: The FeNO test had a remarkable sensitivity of 90.3% for the diagnosis of PCD, and its outcomes were not affected by age, gender, and cardioposition. The saccharin test had a sensitivity of 54.8% and was influenced by age, while not by gender or cardioposition. Although there are more accurate tests for diagnosis of PCD such as TEM and genetic studies, we decided to investigate PCD in children with bronchiectasis by performing two screening tests, NO and saccharin, because of several issues.

scholarly journals Kartagener Syndrome: A Rare Genetic Disorder

2009 ◽  
Vol 48 (173) ◽  
Author(s):  
Kunjan Shakya
Keyword(s):  
Situs Inversus ◽  
Primary Ciliary Dyskinesia ◽  
Autosomal Recessive ◽  
Genetic Disorder ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Kartagener Syndrome ◽  
Irreversible Damage ◽  
History Of ◽  
Ciliary Dyskinesia

Kartagener Syndrome is a rare autosomal recessive disorder consisting of triad of sinusitis, bronchiectasis and situs inversus with dextrocardia. It is the subset of disorder called primary ciliary dyskinesia in which the cilia have abnormal structure and/or function resulting in multisystem diseases of various severity. Clinical manifestations include lifelong, chronic upper and lower respiratory tract diseases secondary to ineffective mucociliary clearance. Early diagnosis and management of chest infections can prevent irreversible damage to lungs and prevent potential lifelong complications. This case report is on a patient who presented with long standing history of sinusitis, bronchiectasis and on examination situs inversus with dextrocardia.Key Words:bronchiectasis, dextrocardia, kartagener syndrome, primary ciliary dyskinesia, situs inversus

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