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We report a novel RPGR missense variant co-segregated with a familial X-linked retinitis pigmentosa (XLRP) case. The brothers were hemizygous for this variant, but only the proband presented with primary ciliary dyskinesia (PCD). Thus, we aimed to elucidate the role of the RPGR variant and other modifier genes in the phenotypic variability observed in the family and its impact on motile cilia. The pathogenicity of the variant on the RPGR protein was evaluated by in vitro studies transiently transfecting the mutated RPGR gene, and immunofluorescence analysis on nasal brushing samples. Whole-exome sequencing was conducted to identify potential modifier variants. In vitro studies showed that the mutated RPGR protein could not localise to the cilium and impaired cilium formation. Accordingly, RPGR was abnormally distributed in the siblings' nasal brushing samples. In addition, a missense variant in CEP290 was identified. The concurrent RPGR variant influenced ciliary mislocalisation of the protein. We provide a comprehensive characterisation of motile cilia in this XLRP family, with only the proband presenting PCD symptoms. The variant's pathogenicity was confirmed, although it alone does not explain the respiratory symptoms. Finally, the CEP290 gene may be a potential modifier for respiratory symptoms in patients with RPGR mutations. [ABSTRACT FROM AUTHOR]

Chronic suppurative otitis media (CSOM) remains a significant clinical challenge in otorhinolaryngology, characterized by prolonged inflammation of the middle ear and mastoid space, accompanied by a perforated tympanic membrane and persistent discharge for a minimum of two weeks. Despite its often viral origin, bacterial colonization is common, with frequent involvement of pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumoniae. CSOM affects over 300 million individuals worldwide, primarily in low socio-economic communities, and is prevalent among children due to acute otitis media (AOM) or congenital disorders. In adults, it is often associated with conditions such as cholesteatoma or polyps. Approximately 60% of CSOM patients suffer from conductive hearing loss, which can impair speech development in children. This review discusses the etiological factors, associated complications, and treatment options for CSOM, emphasizing the importance of accurate diagnosis and comprehensive management, including potential surgical interventions. The persistent and recurrent nature of AOM, anatomical abnormalities, presence of polyps, primary ciliary dyskinesia, and cholesteatoma are highlighted as significant contributors to the development and perpetuation of CSOM. To complete discussion, there is a brief review of management in recovery after elaborated conditions with special regards to returning to physical activities.

Introduction: Primary ciliary dyskinesia (PCD) is caused by the dysfunction of motile cilia resulting in insufficient mucociliary clearance of the lungs. This study aimed to map novel PCD variants and determine their pathogenicity in PCD patients in Kuwait.Methods: Herein, we present five PCD individuals belonging to a cohort of 105 PCD individuals recruited from different hospitals in Kuwait. Genomic DNAs from the family members were analysed to screen for pathogenic PCD variants. Transmission electron microscopy (TEM) and immunofluorescence (IF) analyses were performed on the nasal biopsies to detect specific structural abnormalities within the ciliated cells.Results: Genetic screening and functional analyses confirmed that the five PCD individuals carried novel pathogenic variants of DNAH5 causing PCD in three Arabic families. Of these, one multiplex family with two affected individuals showed two novel homozygous missense variants in DNAH5 causing PCD with situs inversus; another multiplex family with two affected individuals showed two newly identified compound heterozygous variants in DNAH5 causing PCD with situs solitus. In addition, novel heterozygous variants were identified in a child with PCD and situs solitus from a singleton family with unrelated parents. TEM analysis demonstrated the lack of outer dynein arms (ODAs) in all analysed samples, and IF analysis confirmed the absence of the dynein arm component of DNAH5 from the ciliary axoneme.Conclusion: The newly identified pathogenic variants of DNAH5 are associated with PCD as well as variable pulmonary clinical manifestations in Arabic families.

Introduction Sperm immobility is a condition in which sperm are viable but not motile. We reported three patients with sperm immobility, who underwent testicular sperm extraction‐intracytoplasmic sperm injection. Case presentation In case 1, a 32‐year‐old patient with sperm immobility had previously undergone intracytoplasmic sperm injection with ejaculated sperm; however, pregnancy was unsuccessful. testicular sperm extraction‐intracytoplasmic sperm injection was performed at our clinic, and pregnancy was achieved. In case 2, a 23‐year‐old patient with clinical varicocele whose semen analysis revealed sperm immobility underwent varicocelectomy, without improvement. Using the hypo‐osmotic swelling test technique, testicular sperm extraction‐intracytoplasmic sperm injection was performed; however, pregnancy was not achieved. In case 3, a 44‐year‐old patient with sperm immobility underwent testicular sperm extraction, and motile sperm were retrieved. testicular sperm extraction‐intracytoplasmic sperm injection using these sperm resulted in pregnancy. Conclusion Although testicular sperm extraction‐intracytoplasmic sperm injection is not considered a solution in patients with sperm immobility, pregnancies were achieved. testicular sperm extraction‐intracytoplasmic sperm injection may be successful in some cases in which ejaculated sperm intracytoplasmic sperm injection is unsuitable.

Kartagener's syndrome is a subdivision of primary ciliary dyskinesia (PCD)/immotile-cilia syndrome that includes situs inversus, bronchiectasis, sinusitis, and infertility. Although the symptoms appear early, it remains undiagnosed for years. We are reporting an unusual presentation of Kartagener's syndrome as pneumothorax, which has seldom been reported. Kartagener's syndrome presenting as pneumothorax is very unlikely and is one of the rare complications associated with Kartagener's syndrome. Early diagnosis is crucial for preliminary counseling of patients about PCD-associated infertility and to prevent respiratory complications.

Abstract Background The study describes the clinical manifestations and variant screening of two Chinese siblings with primary ciliary dyskinesia (PCD). They carry the same DNAAF2 genotype, which is an extremely rare PCD genotype in the Chinese population. In addition, the study illustrated an overview of published variants on DNAAF2 to date. Methods A two-child family was recruited for the study. Clinical manifestations, laboratory tests, bronchoscopic and otoscopic images, and radiographic data were collected. Whole blood was collected from siblings and their parents for whole-exome sequencing (WES) and Sanger sequencing to screen variants. Results The two siblings exhibited typical clinical manifestations of PCD. Two compound heterozygous variants in DNAAF2 were detected in both by WES. Nonsense variant c.156 C>A and frameshift variant c.177_178insA, which was a novel variant. Conclusion The study identified a novel variant of DNAAF2 in Chinese children with a typical phenotype of PCD, which may enrich our knowledge of the clinical, diagnostic and genetic information of DNAAF2-induced PCD in children.

Digital high-speed videomicroscopy (DHSV) is a crucial tool for evaluating ciliary function in children suspected of primary ciliary dyskinesia (PCD). However, until now, samples are taken without anesthesia due to uncertainty about its effect on ciliary function and DHSV interpretation. This study aimed to investigate the impact of general anesthesia on ciliary functional analysis by DHSV in a series of three patients listed for ENT surgeries, which could improve diagnostic procedures for pediatric patients. Patient 1 (7-year-old girl) underwent adenotonsillectomy and tympanostomy placement tube, while patients 2 (17-month-old boy) and 3 (15-month-old girl) underwent adenoidectomy and tympanostomy placement tube. All patients underwent nasal brushing before general anesthesia (control sample). Experimental samples were taken in the contralateral nostril at the time of equilibration of the anesthetic agents (sevoflurane, propofol, sufentanil). Ciliary beat frequency and pattern were measured using digital high-speed videomicroscopy. Our findings highlighted the variability of respiratory ciliary function under general anesthesia among individuals. Our results emphasize the need for caution when interpreting ciliary function data obtained during general anesthesia. Further research with larger cohorts is warranted for validation.

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disease that develops as a result of ciliary dysfunction, and that presents with clinical findings that may vary depending on the affected system. Situs anomalies are common with PCD. Although approximately half of all cases are associated with situs inversus totalis, they may rarely be associated with situs ambiguous, which is a rare situs anomaly. We share this case of PCD with situs ambiguous due to its rarity. [ABSTRACT FROM AUTHOR]

Background: Primary Ciliary Dyskinesia (PCD) represents a rare condition marked by an abnormal mobility pattern of cilia and flagella, resulting in impaired mucociliary clearance. This deficiency leads to recurrent infections and persistent inflammation of the airways. While previous studies have indicated heightened oxidative stress levels in the exhaled breath condensate of pediatric PCD patients, the assessment of oxidative stress within the affected respiratory tissue remains unexplored. Aims: To assess the oxidative status of human nasal epithelial cells (NECs) in PCD patients. Methods: Thirty-five PCD patients and thirty-five healthy control subjects were prospectively included in the study. Levels of reactive oxygen species (ROS), reactive nitrogen species (RNS), glutathione (GSH), intracellular Ca2+, plasma membrane potential, and oxidative damage in lipids and proteins were measured. In addition, apoptosis and mitochondrial function were analyzed by flow cytometry in NECs. Results: NECs from PCD patients showed reduced levels of apoptosis (p = 0.004), superoxide anion (O2−, p = 0.018), peroxynitrite (ONOO−, p = 0.007), nitric oxide (NO, p = 0.007), mitochondrial hydrogen peroxide (mtH2O2, p < 0.0001), and mitochondrial superoxide anion (mtO2−, p = 0.0004) and increased mitochondrial mass (p = 0.009) compared to those from healthy individuals. No significant differences were observed in oxidized proteins (p = 0.137) and the oxidized/reduced lipid ratio (p = 0.7973). The oxidative profile of NEC cells in PCD patients, according to their ciliary motility, recurrent otitis, recurrent pneumonia, atelectasis, bronchiectasis, and situs inversus, showed no statistically significant differences in the parameters studied. Conversely, patients with chronic rhinosinusitis exhibited lower levels of ONOO− than PCD patients without this condition, with no significant differences related to other symptoms. Conclusions: Our findings strongly suggest the presence of a redox imbalance, specifically leaning toward a reductive state, in PCD patients. [ABSTRACT FROM AUTHOR]

Background: Primary ciliary dyskinesia (PCD) is a genetic ciliopathy characterized by dysfunction of motile cilia. Currently, approximately 50 causative genes accounting for 60%–70% of all PCD cases have been identified in PCD‐affected individuals, but the etiology in approximately 30%–40% of PCD cases remains unknown. Methods: We analyzed the clinical and genetic data of two PCD individuals who were suspected of having PCD. Whole‐exome sequencing and Sanger sequencing were performed to identify and verify the variants in CFAP47. We also evaluated the expression of CFAP47 by real‐time quantitative PCR and immunofluorescence. Transmission electron microscopy in respiratory epithelial cells was also conducted to analyze ciliary function. Results: Two hemizygous missense variants of X‐linked CFAP47 in two unrelated PCD individuals were identified. The expression of CFAP47 in two PCD individuals was significantly reduced in vivo and in vitro assays. A reduction in the amount of epithelial ciliary cells and basal bodies from PCD individuals was also observed. Conclusions: We describe two hemizygous missense variants of X‐linked CFAP47 in two unrelated PCD individuals and prove CFAP47 variants are related to a reduced number of epithelial ciliary cells. Therefore, we suggest that CFAP47 should be known as a novel pathogenic gene of human PCD. [ABSTRACT FROM AUTHOR]

Purpose: To assess the diagnostic potential of whole-exome sequencing (WES) and elucidate the clinical and genetic characteristics of primary ciliary dyskinesia (PCD) in the Korean population. Materials and Methods: Forty-seven patients clinically suspected of having PCD were enrolled at a tertiary medical center. WES was performed in all patients, and seven patients received biopsy of cilia and transmission electron microscopy (TEM). Results: Overall, PCD was diagnosed in 10 (21.3%) patients: eight by WES (8/47, 17%), four by TEM. Among patients diagnosed as PCD based on TEM results, two patients showed consistent results with WES and TEM of PCD (2/4, 50%). In addition, five patients, who were not included in the final PCD diagnosis group, had variants of unknown significance in PCD-related genes (5/47, 10.6%). The most frequent pathogenic (P)/likely pathogenic (LP) variants were detected in DNAH11 (n=4, 21.1%), DRC1 (n=4, 21.1%), and DNAH5 (n=4, 21.1%). Among the detected 17 P/LP variants in PCD-related genes in this study, 8 (47.1%) were identified as novel variants. Regarding the genotype-phenotype correlation in this study, the authors experienced severe PCD cases caused by the LP/P variants in MCIDAS, DRC1, and CCDC39. Conclusion: Through this study, we were able to confirm the value of WES as one of the diagnostic tools for PCD, which increases with TEM, rather than single gene tests. These results will prove useful to hospitals with limited access to PCD diagnostic testing but with relatively efficient in-house or outsourced access to genetic testing at a pre-symptomatic or early disease stage. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are associated with sleep disturbances affecting quality of life (QOL) in both children and adults. However, little is known about the progression of these complaints over time, and the effect of CFTR modulator (CFTRm) therapies. Participants completed sleep quality (SDSC, PSQI) and quality of life questionnaires (PedQL, QOL-BE) as well as the Epworth sleepiness scale (ESS) at baseline and after 4 years. Medical records were reviewed for clinical data and correlations were sought between sleep, QOL, and clinical parameters. A total of 67 patients (33 pediatric), 37 pancreatic insufficient CF (CF-PI), 15 pancreatic sufficient CF (CF-PS), and 15 PCD patients, completed the study. In adults, global sleep quality decreased from 85.8% (76.2–90.5) to 80.9% (71.4–85.7); (p = 0.009). Analysis by disease cohort showed a significant deterioration only in the CF-PS group. In adults off CFTRm, sleep quality decreased from 85.7% (78.6–88.2) to 80.9% (71.4–87.3); (p = 0.021) and from 85.8% (76.2–92.9) to 76.2% (71.4–85.8); (p = 0.078) in people on CFTRm. Changes in sleep quality and changes in QOL over time were strongly associated with each other. In conclusion sleep quality deteriorates over time, correlates with QOL, and is driven primarily by adults and CF-PS patients. CFTRm has a possible effect on sleep initiation; however, results are mixed, and further long-term studies are required. [ABSTRACT FROM AUTHOR]

More and more attention is paid to diseases such as internal transfer and brain malformation which are caused by the abnormal morphogenesis of cilia. These cilia‐related diseases are divided into two categories: ciliopathy resulting from defects of primary cilia and primary ciliary dyskinesia (PCD) caused by functional dysregulation of motile cilia. Cilia are widely distributed, and their related diseases can cover many human organs and tissues. Recent studies prove that primary cilia play a key role in maintaining homeostasis in the cardiovascular system. However, molecular mechanisms of cilia‐related diseases remain elusive. Here, we reviewed recent research progresses on characteristics, molecular mechanisms and treatment methods of ciliopathy and PCD. Our review is beneficial to the further research on the pathogenesis and treatment strategies of cilia‐related diseases. [ABSTRACT FROM AUTHOR]

Background: The study describes the clinical manifestations and variant screening of two Chinese siblings with primary ciliary dyskinesia (PCD). They carry the same DNAAF2 genotype, which is an extremely rare PCD genotype in the Chinese population. In addition, the study illustrated an overview of published variants on DNAAF2 to date. Methods: A two-child family was recruited for the study. Clinical manifestations, laboratory tests, bronchoscopic and otoscopic images, and radiographic data were collected. Whole blood was collected from siblings and their parents for whole-exome sequencing (WES) and Sanger sequencing to screen variants. Results: The two siblings exhibited typical clinical manifestations of PCD. Two compound heterozygous variants in DNAAF2 were detected in both by WES. Nonsense variant c.156 C>A and frameshift variant c.177_178insA, which was a novel variant. Conclusion: The study identified a novel variant of DNAAF2 in Chinese children with a typical phenotype of PCD, which may enrich our knowledge of the clinical, diagnostic and genetic information of DNAAF2-induced PCD in children. [ABSTRACT FROM AUTHOR]

Eosinophilic otitis media (EOM) is a rare middle ear disease with unfavorable outcomes. Under the current diagnostic criteria of EOM, it is challenging to suspect EOM before tympanostomy. Therefore, this study attempted to use blood eosinophil levels for the differential diagnosis of EOM from other conditions. Three disease groups with features of recurrent otorrhea were categorized, which included the following: EOM (n = 9), granulomatosis with polyangiitis (GPA, n = 12), and primary ciliary dyskinesia (PCD, n = 6). Clinical and radiological characteristics were analyzed in the three groups. Patients who underwent ventilation tube insertion due to serous otitis media were enrolled as the control group (n = 225) to evaluate the diagnostic validity of blood eosinophilia. The EOM group showed a significantly higher blood eosinophil concentration (p < 0.001) and blood eosinophil count (p < 0.001) compared to the GPA and PCD groups. The estimated sensitivity and specificity for diagnosing EOM from OME patients who underwent ventilation tube insertion were 100% and 95.6%, respectively. In addition, EOM tended to have protympanic space soft tissue density and a relatively clear retrotympanic space in temporal bone computerized tomography. Blood eosinophil evaluation is a significant clinical indicator of EOM. Furthermore, the assessment of exclusive protympanic soft tissue density can provide an additional diagnostic clue. [ABSTRACT FROM AUTHOR]

Ciliopathies responsible for retinitis pigmentosa can also cause systemic manifestations. RPGR is a ciliary gene and pathogenic variants in RPGR cause a retinal ciliopathy, the commonest cause of X-linked recessive retinitis pigmentosa. The RPGR protein interacts with numerous other ciliary proteins present in the transition zone of both motile and sensory cilia, and may play an important role in regulating ciliary protein transport. There has been a growing, putative association of RPGR variants with systemic ciliopathies: mainly sino-respiratory infections and primary ciliary dyskinesia. Retrospective case series of patients with RPGR-RP presenting to Oxford Eye Hospital with systemic disease. We report three children with RPGR-related rod-cone dystrophy, all of whom have mutations in the N-terminus of RPGR. Two cases co-presented with confirmed diagnoses of primary ciliary dyskinesia and one case with multiple sino-respiratory symptoms strongly suggestive of primary ciliary dyskinesia. These and all previously reported RPGR co-pathologies relate to ciliopathies and have no other systemic associations. The link between RPGR variants and a systemic ciliopathy remains plausible, but currently unproven. [ABSTRACT FROM AUTHOR]

Bronchiectasis is a chronic respiratory condition characterized by irreversible bronchial dilation, often caused by infection or inflammation. It can be associated with primary ciliary dyskinesia (PCD), a hereditary disorder affecting cilia function in various organs and flagella. PCD's genetic heterogeneity leads to varying disease severity. PCD may be more prevalent in Asia, but its diagnosis is often delayed in Japan. This study reviewed a case of PCD and retinitis pigmentosa (RP) with the relevant literature. The patient had a persistent cough, sputum, and diffuse bronchiectasis. He was diagnosed with a combination of PCD and RP, with the presence of an X‐linked retinitis pigmentosa GTPase regulator (RPGR) variant confirmed through electron microscopy, retinal scan, and genetic testing. Although co‐occurrence of bronchiectasis and RP is rare, PCD should be considered in cases of persistent wet cough in childhood or unidentified bronchiectasis aetiology. Ophthalmologists should consider concomitant PCD in RP patients. [ABSTRACT FROM AUTHOR]

Primary ciliary dyskinesia (PCD) is a highly heterogeneous recessive inherited disorder. FAP54, the homolog of CFAP54 in Chlamydomonas reinhardtii, was previously demonstrated as the C1d projection of the central microtubule apparatus of flagella. A Cfap54 knockout mouse model was then reported to have PCD-relevant phenotypes. Through whole-exome sequencing, compound heterozygous variants c.2649_2657delinC (p. E883Dfs*47) and c.7312_7313insCGCAGGCTGAATTCTTGG (p. T2438delinsTQAEFLA) in a new suspected PCD-relevant gene, CFAP54, were identified in an individual with PCD. Two missense variants, c.4112A>C (p. E1371A) and c.6559C>T (p. P2187S), in CFAP54 were detected in another unrelated patient. In this study, a minigene assay was conducted on the frameshift mutation showing a reduction in mRNA expression. In addition, a CFAP54 in-frame variant knock-in mouse model was established, which recapitulated the typical symptoms of PCD, including hydrocephalus, infertility, and mucus accumulation in nasal sinuses. Correspondingly, two missense variants were deleterious, with a dramatic reduction in mRNA abundance from bronchial tissue and sperm. The identification of PCD-causing variants of CFAP54 in two unrelated patients with PCD for the first time provides strong supportive evidence that CFAP54 is a new PCD-causing gene. This study further helps expand the disease-associated gene spectrum and improve genetic testing for PCD diagnosis in the future. [ABSTRACT FROM AUTHOR]

Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder characterized by alterations in motile cilia function. The diagnosis of PCD is challenging due to the lack of standardized methods in clinical practice. High-speed video microscopy analysis (HSVA) directly evaluates ciliary beat frequency (CBF) in PCD. Recently, open-source ciliary analysis software applications have shown promise in measuring CBF accurately. However, there is limited knowledge about the performance of different software applications, creating a gap in understanding their comparative effectiveness in measuring CBF in PCD. We compared two open-source software applications, CiliarMove (v219) and Cilialyzer (v1.2.1-b3098cb), against the manual count method. We used high-speed videos of nasal ciliary brush samples from PCD RSPH4A-positive (PCD (RSPH4A)) patients and healthy controls. All three methods showed lower median CBF values for patients with PCD (RSPH4A) than in healthy controls. CiliarMove and Cilialyzer identified lower CBF in patients with PCD (RSPH4A), similarly to the manual count. Cilialyzer, CiliarMove, and manual count methods demonstrated statistical significance (p-value < 0.0001) in the difference of median CBF values between patients with PCD (RSPH4A) and healthy controls. Correlation coefficients between the manual count values against both software methods demonstrated positive linear relationships. These findings support the utility of open-source software-based analysis tools. Further studies are needed to validate these findings with other genetic variants and identify the optimal software for accurate CBF measurement in patients with PCD.

Defects in motile cilia, termed motile ciliopathies, result in clinical manifestations affecting the respiratory and reproductive system, as well as laterality defects and hydrocephalus. We previously defined biallelic MNS1 variants causing situs inversus and male infertility, mirroring the findings in Mns1−/− mice. Here, we present clinical and genomic findings in five newly identified individuals from four unrelated families affected by MNS1-related disorder. Ciliopathy panel testing and whole exome sequencing identified one previously reported and two novel MNS1 variants extending the genotypic spectrum of disease. A broad spectrum of laterality defects including situs inversus totalis and heterotaxia was confirmed. Interestingly, a single affected six-year-old girl homozygous for an MNS1 nonsense variant presented with a history of neonatal respiratory distress syndrome, recurrent respiratory tract infections, chronic rhinitis, and wet cough. Accordingly, immunofluorescence analysis showed the absence of MNS1 from the respiratory epithelial cells of this individual. Two other individuals with hypomorphic variants showed laterality defects and mild respiratory phenotype. This study represents the first observation of heterotaxia and respiratory disease in individuals with biallelic MNS1 variants, an important extension of the phenotype associated with MNS1-related motile ciliopathy disorder.

Odad3 gene loss-of-function mutation leads to Primary Ciliary Dyskinesia (PCD), a disease caused by motile cilia dysfunction. Previously, we demonstrated that knockout of the Odad3 gene in mice replicates several features of PCD, such as hydrocephalus, defects in left–right body symmetry, and male infertility, with a complete absence of sperm in the reproductive tract. The majority of Odad3 knockout animals die before sexual maturation due to severe hydrocephalus and failure to thrive, which precludes fertility studies. Here, we performed the expression analysis of the Odad3 gene during gonad development and in adult testes. We showed that Odad3 starts its expression during the first wave of spermatogenesis, specifically at the meiotic stage, and that its expression is restricted to the germ cells in the adult testes, suggesting that Odad3 plays a role in spermatozoa formation. Subsequently, we conditionally deleted the Odad3 gene in adult males and demonstrated that even partial ablation of the Odad3 gene leads to asthenoteratozoospermia with multiple morphological abnormalities of sperm flagella (MMAF) in mice. The analysis of the seminiferous tubules in Odad3-deficient mice revealed defects in spermatogenesis with accumulation of seminiferous tubules at the spermiogenesis and spermiation phases. Furthermore, analysis of fertility in heterozygous Odad3+/− knockout mice revealed a reduction in sperm count and motility as well as abnormal sperm morphology. Additionally, Odad3+/− males exhibited a shorter fertile lifespan. Overall, these results suggest the important role of Odad3 and Odad3 gene dosage in male fertility. These findings may have an impact on the genetic and fertility counseling practice of PCD patients carrying Odad3 loss-of-function mutations.

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous, motile ciliopathy, characterized by neonatal respiratory distress, recurrent upper and lower respiratory tract infections, subfertility, and laterality defects. Diagnosis relies on a combination of tests for confirmation, including nasal nitric oxide (nNO) measurements, high-speed videomicroscopy analysis (HSVMA), immunofluorescent staining, axonemal ultrastructure analysis via transmission electron microscopy (TEM), and genetic testing. Notably, there is no single gold standard confirmatory or exclusionary test. Currently, 54 causative genes involved in cilia assembly, structure, and function have been linked to PCD; this rare disease has a spectrum of clinical manifestations and emerging genotype–phenotype relationships. In this review, we provide an overview of the structure and function of motile cilia, the emerging genetics and pathophysiology of this rare disease, as well as clinical features associated with motile ciliopathies, novel diagnostic tools, and updates on genotype–phenotype relationships in PCD.

We aimed to assess anxiety of children with primary ciliary dyskinesia (PCD) and their primary caregivers at the beginning of Coronavirus disease-2019 (COVID-19) pandemic and change in levels of anxiety in first year with prolongation of pandemic. This was a two-step study; first step was questionnaire-based, conducted via teleconference. In first step, 29 patients and 105 healthy children and their mothers were participated; 25 children with PCD and their mothers were in second step. Demographic characteristics, clinical informations were recorded. Children’s and mothers’ state and trait anxiety levels were assessed and compared. Anxiety levels of mothers of patients were assessed according to clinical characteristics of children. Mothers’ knowledge of COVID-19 and effect of teleconference on their anxiety was evaluated. State anxiety levels in the first year of pandemic of children with PCD and their mothers were also compared. Compared to control group, state anxiety of children in 13-18 age group and trait anxiety of their mothers were lower (p

Abstract Background LRRC6 is an assembly factor for dynein arms in the cytoplasm of motile ciliated cells, and when mutated, dynein arm components remained in the cytoplasm. Here, we demonstrate the role of LRRC6 in the active nuclear translocation of FOXJ1, a master regulator for cilia-associated gene transcription. Methods We generated Lrrc6 knockout (KO) mice, and we investigated the role of LRRC6 on ciliopathy development by using proteomic, transcriptomic, and immunofluorescence analysis. Experiments on mouse basal cell organoids confirmed the biological relevance of our findings. Results The absence of LRRC6 in multi-ciliated cells hinders the assembly of ODA and IDA components of cilia; in this study, we showed that the overall expression of proteins related to cilia decreased as well. Expression of cilia-related transcripts, specifically ODA and IDA components, dynein axonemal assembly factors, radial spokes, and central apparatus was lower in Lrrc6 KO mice than in wild-type mice. We demonstrated that FOXJ1 was present in the cytoplasm and translocated into the nucleus when LRRC6 was expressed and that this process was blocked by INI-43, an importin α inhibitor. Conclusions Taken together, these results hinted at the LRRC6 transcriptional regulation of cilia-related genes via the nuclear translocation of FOXJ1. Video Abstract

BackgroundThe mutations in the RPGR (retinitis pigmentosa GTPase regulator) gene are the most common cause of X-linked retinitis pigmentosa (XLRP), a rare genetic disorder affecting the photoreceptor cells in the retina. Several reported cases identified this gene as a genetic link between retinitis pigmentosa (RP) and primary ciliary dyskinesia (PCD), characterised by impaired ciliary function predominantly in the respiratory tract. Since different mutations in the same gene can result in various clinical manifestations, it is important to describe a correlation between the gene variant and the observed phenotype.MethodsTwo young brothers from a non-consanguineous Slovak family with diagnosed retinal dystrophy and recurrent respiratory infections were examined. Suspected PCD was diagnosed based on a PICADAR questionnaire, nasal nitric oxide analysis, transmission electron microscopy, high-speed video microscopy analysis, and genetic testing.ResultsWe identified a novel frameshift RPGR mutation NM_001034853: c.309_310insA, p.Glu104Argfs*12, resulting in a complex X-linked phenotype combining PCD and RP. In our patients, this mutation was associated with normal ultrastructure of respiratory cilia, reduced ciliary epithelium, more aciliary respiratory epithelium, shorter cilia, and uncoordinated beating with a frequency at a lower limit of normal beating, explaining the clinical manifestation of PCD in our patients.ConclusionThe identified novel pathogenic mutation in the RPGR gene expands the spectrum of genetic variants associated with the X-linked PCD phenotype overlapping with RP, highlighting the diversity of mutations contributing to the disorder. The described genotype–phenotype correlation can be useful in clinical practice to recognise a broader spectrum of PCD phenotypes as well as for future research focused on the genetic basis of PCD, gene interactions, the pathways implicated in PCD pathogenesis, and the role of RPGR protein for the proper functioning of cilia in various tissues throughout the body.

ObjectiveCardiac surgery in Congenital Heart Disease-Heterotaxy (CHD-HTX) patients often leads to increased postoperative airway complications. Abnormal respiratory ciliary function, resembling primary ciliary dyskinesia, has been observed. We expanded the sample size by retrospectively reviewing Ciliary Dysfunction (CD) in CHD-HTX patients to verify the increased risk of post-surgical respiratory complications.MethodsWe conducted a retrospective review of 69 CHD-HTX patients undergoing cardiac surgery, assessing abnormal respiratory function using nasal nitric oxide (nNO) levels and nasal ciliary motion observed in video microscopy. Data collected included demographics, surgical details, postoperative complications, length of stay, ICU hours, salvage procedures, intubation duration, and mortality.ResultsThe CD and no-CD cohorts exhibited notable similarities in risk adjustment in Congenital Heart Surgery-1 (RACHS-1) risk categories, age at the time of surgery, and the duration of follow-up evaluations. We observed a trend toward an increased length of post-operative stay in the CD group (15.0 vs. 14.0; P = 0.0017). CHD-HTX patients with CD showed significantly higher rates of respiratory complications (70% vs. 44.4%; P = 0.008). There were no notable variances observed in postoperative hospitalization duration, mechanical ventilation period, or surgical mortality.ConclusionOur findings suggest that CHD-HTX patients with CD may face an elevated risk of respiratory complications. These results offer guidance for perioperative management and serve as a reference for further pathological studies.

ABSTRACT Primary ciliary dyskinesia (PCD) is characterized by symptoms such as productive cough, rhinitis, and recurrent infections in both the upper and lower airways, which can lead to chronic infection, bronchiectasis, and decreased pulmonary function. Our study aimed to analyze the diversity and composition of the microbiota in the respiratory tract and investigate the correlation of the microbiota with pulmonary exacerbation in PCD patients. This study employed 16S rRNA amplicon sequencing to explore the microbiota present in both bronchoalveolar lavage fluid (BALF) and sputum samples collected from PCD patients. Eighty-five airway samples (17 BALF and 68 sputum samples) were collected from 72 patients aged 2 months to 60 years. Significantly lower sputum microbiota diversity and richness were found in the pulmonary exacerbation group than in the pulmonary stabilization group; additionally, the relative abundance of Pseudomonas increased when pulmonary exacerbation occurred. There was a positive correlation between pulmonary exacerbation and the relative abundance of Pseudomonas, while Streptococcus, Moraxella, and Haemophilus showed a negative correlation. Although there was no significant difference in the sputum microbiota diversity and composition in children aged 6–18 years with pulmonary exacerbation, Pseudomonas increased during pulmonary exacerbation. BALF samples of pediatric patients with pulmonary exacerbation had a lower microbiota diversity and richness; furthermore, Pseudomonas had a higher abundance and a moderate distinguishing effect. We found that microbiota beta diversity and dominance were decreased during pulmonary exacerbation. Additionally, Pseudomonas had a higher abundance and moderate distinguishing effect in pediatric patients with pulmonary exacerbation. IMPORTANCE PCD is a rare disease characterized by productive cough, rhinitis, and recurrent infections of the upper and lower airways. Because the diagnosis of PCD is often delayed, patients receive more antibiotics, experience a heavier financial burden, and have a worse prognosis; thus, it is very important to identify the pathogeny and use the correct antibiotic. In this large single-center study of PCD microbiota, we identified an outline of the bacterial microbes from the respiratory tract; furthermore, we found that the microbiota diversity in pediatric sputum was richer than that in pediatric BALF through sequencing, indicating a heterogeneous community structure. The microbiota diversity and richness were lower during pulmonary exacerbation than during pulmonary stabilization. A significantly higher abundance of Pseudomonas had a moderate distinguishing effect for lung exacerbation, which attracted more attention for the study of Pseudomonas therapy in pediatric patients with PCD.

Abstract Bronchiectasis is a chronic respiratory condition characterized by irreversible bronchial dilation, often caused by infection or inflammation. It can be associated with primary ciliary dyskinesia (PCD), a hereditary disorder affecting cilia function in various organs and flagella. PCD's genetic heterogeneity leads to varying disease severity. PCD may be more prevalent in Asia, but its diagnosis is often delayed in Japan. This study reviewed a case of PCD and retinitis pigmentosa (RP) with the relevant literature. The patient had a persistent cough, sputum, and diffuse bronchiectasis. He was diagnosed with a combination of PCD and RP, with the presence of an X‐linked retinitis pigmentosa GTPase regulator (RPGR) variant confirmed through electron microscopy, retinal scan, and genetic testing. Although co‐occurrence of bronchiectasis and RP is rare, PCD should be considered in cases of persistent wet cough in childhood or unidentified bronchiectasis aetiology. Ophthalmologists should consider concomitant PCD in RP patients.

Introduction Purpose Methods Results Conclusion Kartagener’s syndrome (KS), consisting of bronchiectasis, situs inversus totalis, and sinusitis, is a subtype of primary ciliary dyskinesia (PCD). The presence of KS may affect respiratory and physical functions.This study aimed to compare respiratory functions, exercise capacity, muscle strength, and physical activity levels among children with PCD with/without KS and healthy peers.Fifteen patients with KS, 23 with PCD without KS, and 27 controls were compared. Pulmonary function, functional exercise capacity (6-minute walk test − 6MWT), maximal inspiratory, expiratory (MIP, MEP), and skeletal muscle strength, inspiratory muscle endurance (IME), and physical activity level were evaluated.The forced expiratory volume in one second (FEV1) % (p = .009), forced expiratory flow from 25%-75% (FEF25–75%) % (p = .001), MIP (p = .034), MEP (p = .003), 6MWT distance (p = .001), and daily steps (p = .034) were significantly different among the groups. Quadriceps femoris (QF) muscle strength and IME were similar in groups (p ˃ .05). FEV1% (p = .002), FEF25–75% % (p = .001), MIP (p = .027), MEP (p = .001), and 6MWT distance (p = .003) in patients with KS; 6MWT distance (p = .003) in patients with PCD without KS was significantly lower than controls.The presence of KS affects pulmonary function, respiratory muscle strength, and physical activity more. Exercise capacity and physical activity levels are decreased, inspiratory muscle endurance and QF muscle strength are preserved in patients with KS and PCD without KS. Kartagener’s syndrome further impairs pulmonary and extrapulmonary outcomes; the reasons should be investigated, and the necessity of rehabilitation approaches that will prevent deterioration come to the fore. [ABSTRACT FROM AUTHOR]

Whole-exome sequencing has expedited the diagnostic work-up of primary ciliary dyskinesia (PCD), when used in addition to clinical phenotype and nasal nitric oxide. However, it reveals variants of uncertain significance (VUS) in established PCD genes or (likely) pathogenic variants in genes of uncertain significance in approximately 30% of tested individuals. We aimed to assess genotype–phenotype correlations in adults with bronchiectasis, clinical suspicion of PCD, and inconclusive whole-exome sequencing results using transmission electron microscopy (TEM) and ciliary image averaging by the PCD Detect software. We recruited 16 patients with VUS in CCDC39, CCDC40, CCDC103, DNAH5, DNAH5/CCDC40, DNAH8/HYDIN, DNAH11, and DNAI1 as well as variants in the PCD candidate genes DNAH1, DNAH7, NEK10, and NME5. We found normal ciliary ultrastructure in eight patients with VUS in CCDC39, DNAH1, DNAH7, DNAH8/HYDIN, DNAH11, and DNAI1. In six patients with VUS in CCDC40, CCDC103, DNAH5, and DNAI1, we identified a corresponding ultrastructural hallmark defect. In one patient with homozygous variant in NME5, we detected a central complex defect supporting clinical relevance. Using TEM as a targeted approach, we established important genotype–phenotype correlations and definite PCD in a considerable proportion of patients. Overall, the PCD Detect software proved feasible in support of TEM. [ABSTRACT FROM AUTHOR]

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder caused by defects in motile ciliary function and/or structure. Outer dynein arm docking complex subunit 1 (ODAD1) is an important component of the outer dynein arm docking complex (ODA-DC). To date, 13 likely pathogenic mutations of ODAD1 have been reported. However, the pathogenesis of ODAD1 mutations remains elusive. To investigate the pathogenesis of splice-site mutations in ODAD1 discovered in this study and those reported previously, molecular and functional analyses were performed. Whole-exome sequencing revealed a compound mutation in ODAD1 (c.71-2A>C; c.598-2A>C) in a patient with PCD, with c.598-2A>C being a novel mutation that resulted in two mutant transcripts. The compound mutation in ODAD1 (c.71-2A>C; c.598-2A>C) led to aberrant splicing that resulted in the absence of the wild-type ODAD1 and defects of the outer dynein arm in ciliary axonemes, causing a decrease in ciliary beat frequency. Furthermore, we demonstrated that the truncated proteins resulting from splice- site mutations in ODAD1 could retain partial function and inhibit the interaction between wild-type ODAD1 and ODAD3. The results of this study expand the mutational and clinical spectrum of PCD, provide more evidence for genetic counseling, and offer new insights into gene-based therapeutic strategies for PCD. [ABSTRACT FROM AUTHOR]

Key points: Our findings suggest that primary ciliary dyskinesia (PCD)‐related chronic rhinosinusitis (CRS) has a more significant impact on quality of life than CRS without nasal polyps and cystic fibrosis (CF).PCD and CF have similar mucociliary clearance defects, yet sinonasal symptom severity varies between the two. [ABSTRACT FROM AUTHOR]

Objective: This study explored the clinical features and immune responses of children with primary ciliary dyskinesia (PCD) during pneumonia episodes. Methods: The 61 children with PCD who were admitted to hospital because of pneumonia were retrospectively enrolled into this study between April 2017 and August 2022. A total of 61 children with pneumonia but without chronic diseases were enrolled as the control group. The clinical characteristics, levels of inflammatory indicators, pathogens, and imaging features of the lungs were compared between the two groups. Results: The PCD group had higher levels of lymphocytes (42.80% versus 36.00%, p = 0.029) and eosinophils (2.40% versus 1.25%, p = 0.020), but lower neutrophil counts (3.99 versus 5.75 × 109/L, p = 0.011), percentages of neutrophils (46.39% versus 54.24%, p = 0.014), CRP (0.40 versus 4.20 mg/L, p < 0.001) and fibrinogen (257.50 versus 338.00 mg/dL, p = 0.010) levels. Children with PCD and children without chronic diseases were both most commonly infected with Mycoplasma pneumoniae (24.6% versus 51.9%). Children with PCD had significantly more common imaging features, including mucous plugging (p = 0.042), emphysema (p = 0.007), bronchiectasis (p < 0.001), mosaic attenuation (p = 0.012), interstitial inflammation (p = 0.015), and sinusitis (p < 0.001). Conclusion: PCD is linked to immune system impairment, which significantly contributes to our understanding of the pathophysiology of this entity. [ABSTRACT FROM AUTHOR]

Introduction: Primary ciliary dyskinesia (PCD) is a congenital thoracic disorder caused by dysfunction of motile cilia, resulting in insufficient mucociliary clearance of the lungs. The overall aim of this study is to identify causative defective genes in PCD-affected individuals in the Kuwaiti population. Methods: A cohort of multiple consanguineous PCD families was identified from Kuwaiti patients and genomic DNA from the family members was isolated using standard procedures. The DNA samples from all affected individuals were analyzed by whole exome sequencing (WES). Transmission electron microscopy (TEM) and immunofluorescent analysis (IF) were performed on samples obtained by nasal brushings to identify specific structural abnormalities within ciliated cells. Results: Here, we present six multiplex families with 11 patients who all presented with typical PCD symptoms. Ten out of eleven patients inherited a 3 bp homozygous deletion of GAA in RSPH9, whereas the eleventh patients inherited this variant in trans with a frameshift deletion in RSPH9. Genetic results were confirmed by segregation analysis. The in-frame deletion of GAA in RSPH9 has previously been published as pathogenic in both annotated RSPH9 transcript variants (1 and 2). In contrast, the previously unpublished RSPH9 frameshift deletion identified in KU-15.IV2 impacts only RSPH9 transcript variant two. Regarding all 11 PCD individuals analyzed, IF results demonstrated absence of RSPH9 protein and TEM analysis showed the typical findings in RSPH9 mutant individuals. Conclusions: We present the largest cohort of PCD individuals affected by the founder in-frame deletion GAA in RSPH9. This founder variant is the most common PCD-causing variant in Bedouin Arabs in Kuwait. [ABSTRACT FROM AUTHOR]

Nasal nitric oxide (nNO) is a gas synthesized by the inducible and constitutive NO synthase (NOS) enzyme in the airway cells of the nasal mucosa. Like lung nitric oxide, it is thought to be associated with airway inflammation in various respiratory diseases in children. The aim of our review was to investigate the current state of use of nNO measurement in children. A comprehensive search was conducted using the Web of Science and PubMed databases specifically targeting publications in the English language, with the following keywords: nasal NO, children, allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD), and cystic fibrosis (CF). We describe the use of nNO in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, PCD, and CF based on the latest literature. nNO is a noninvasive, clinically applicable test for use in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, PCD, and CF. It can be used as a complementary method in the diagnosis of these respiratory diseases and as a monitoring method for the treatment of allergic rhinitis and acute and chronic rhinosinusitis. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are genetic respiratory diseases featured by chronic upper and lower airway inflammation and infection, mainly due to impaired mucociliary clearance due to genetic mutations. Sleep is crucial to healthy children's normal physical and psychological development and has an important value in chronic respiratory diseases. Impaired sleep quality, such as sleep deprivation or insufficient sleep during the night, and sleep respiratory disorders (SRDs) are common in 5% to 30% of the general population. Sleep disruption leads to attention deficits, daytime sleepiness, fatigue and mood disorders and correlates to a worsened quality of life. Furthermore, sleep respiratory disorders (SRSs) are under-recognized comorbidities in CF and PCD patients. SRSs include a spectrum of symptoms ranging from primary snoring through upper airway resistance to obstructive sleep apnea (OSA), nocturnal hypoventilation and hypoxemia occurring in people with moderate to severe lung disease and damaging the disease-related outcomes and quality of life. Effective screening during sleep with polysomnography is very important for the timely initiation of efficacious treatments and to prevent worsened respiratory, metabolic and cardiovascular outcomes. However, the impact of SRDs on health and quality of life is still underinvestigated. [ABSTRACT FROM AUTHOR]

Background: Primary ciliary dyskinesia (PCD, MIM 244400) is an inherited ciliopathy disorder characterized by recurrent sinopulmonary infections, subfertility, and laterality defects. The true incidence of PCD in Saudi Arabia is not known, but it is likely underdiagnosed due to the high prevalence of consanguineous marriages. In this study, we aim to study the clinical and genetic characteristics of PCD patients in the southwestern region of Saudi Arabia to provide guidance to clinicians and researchers studying PCD. Methods: This was a cross-sectional study conducted between 2019 and 2023 in Abha Maternity and Children's Hospital. Twenty-eight patients with clinically diagnosed PCD were recruited. The diagnosis of PCD was confirmed via whole-exome sequencing. Results: A total of 28 patients from 20 families were identified and recruited for this study. The median age of patients was 7.5 years (IQR = 3, 13 years). The people of different sexes were evenly distributed, and 18 patients (64%) had neonatal respiratory distress (NRD). The median age of diagnosis was 5.5 years (IQR = 2, 11 years), while the age when the first symptoms appeared was 3 months old (IQR = 1, 6 months). The prevalence of a chronic wet cough, chronic rhinosinusitis, ear infections were 100% (n = 28), 78.6% (n = 22), and 67.9% (19), respectively. The most common gene in our study was DNAH5, which represented 17.9% (five out of twenty-eight) of the cases. Furthermore, the remaining pathogenic variants included: 14.3% with RSPH9 in four individuals (three families), 14.3% with DNAI2 in four individuals (two families), and 10.7% with LRRC56 in three individuals (one family). The most common findings on the chest CT scans were consolidation (seen in all patients), mucus plugging (seen in 95%), and bronchiectasis (seen in 77%). In the patients with bronchiectasis, the most commonly affected lobes were the right lower lobe (88%) and left lower lobe (76%). The patients with PCD and situs inversus were more likely to experience NRD than the patients with PCD and situs solitus. The median PICADAR score in the patients with PCD and situs inversus (median: 11.5; Q1: 10–Q3: 12.5) was significantly higher compared to those with PCD and situs solitus (median: 7.5; Q1: 5.8–Q3: 8) (U = 10.5; p < 0.001). Conclusion: This study provides preliminary data on the clinical and genetic characteristics of PCD patients in the southwestern region of Saudi Arabia. We found that DNAH5 and RSPH9 genes were the most common genes among the studied population. Furthermore, PCD should be considered for each child with early NRD and laterality defects, and further confirmatory tests are recommended. These findings also highlight the need for greater awareness of the disease in daily clinical practice to facilitate early diagnosis and avoid irreversible lung damage. [ABSTRACT FROM AUTHOR]

Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD. [ABSTRACT FROM AUTHOR]

Low nasal nitric oxide (nNO) is a typical feature of Primary Ciliary Dyskinesia (PCD). nNO is part of the PCD diagnostic algorithm due to its discriminative power against other lung diseases, such as cystic fibrosis (CF). However, the underlying pathomechanisms are elusive. To better understand NO dysregulation in PCD, the L-arginine/NO (Arg/NO) pathway in patients with PCD (pwPCD) and CF (pwCF) and in healthy control (HC) subjects was investigated. In a prospective, controlled study, we measured in 24 pwPCD, 25 age-matched pwCF, and 14 HC the concentrations of the NO precursors Arg and homoarginine (hArg), the arginase metabolite ornithine (Orn), the NO inhibitor asymmetric dimethylarginine (ADMA), and the major NO metabolites (nitrate, nitrite) in sputum, plasma, and urine using validated methods. In comparison to HC, the sputum contents (in µmol/mg) of L-Arg (PCD 18.43 vs. CF 329.46 vs. HC 9.86, p < 0.001) and of ADMA (PCD 0.055 vs. CF 0.015 vs. HC 0.010, p < 0.001) were higher. In contrast, the sputum contents (in µmol/mg) of nitrate and nitrite were lower in PCD compared to HC (nitrite 4.54 vs. 9.26, p = 0.023; nitrate 12.86 vs. 40.33, p = 0.008), but higher in CF (nitrite 16.28, p < 0.001; nitrate 56.83, p = 0.002). The metabolite concentrations in urine and plasma were similar in all groups. The results of our study indicate that PCD, unlike CF, is associated with impaired NO synthesis in the lung, presumably due to mechano-chemical uncoupling. [ABSTRACT FROM AUTHOR]

Primary ciliary dyskinesia is a heterogeneous, inherited motile ciliopathy in which respiratory cilia beat abnormally, and some ultrastructural ciliary defects and specific genetic mutations have been associated with particular ciliary beating alterations. Ciliary beating can be evaluated using digital high-speed videomicroscopy (DHSV). However, normal reference values, essential to assess ciliary beating in patients referred for a PCD diagnostic, vary between centres, as minor variations in protocols might influence ciliary beating. Consequently, establishment of normal values is essential for each PCD diagnostic centre. We aimed to evaluate whether delay after sampling, and temperature for conservation of respiratory ciliated samples, might modify assessments of ciliary beating. In total, 37 healthy nasal brushing samples of respiratory ciliated epithelia were collected. Video sequences were recorded at 37 °C immediately using DHSV. Then, the samples were divided and conserved at 4 °C or at room temperature (RT). Ciliated beating edges were then recorded at 37 °C, at 3 h and at 9 h post sampling. In six samples, recordings were continued up to 72 h after sampling. Ciliary beating was assessed manually by ciliary beat frequency (CBFM) and ciliary beat pattern (CBP). A semi-automatic software was used for quantitative analysis. Both CBF and CBP evaluated manually and by a semi-automated method were stable 9 h after sampling. CBFM was higher when evaluated using samples stored at RT than at 4 °C. CBP and the semi-automated evaluation of ciliary beating were not affected by storage temperature. When establishing normal references values, ciliary beating can be evaluated at 37 °C up to 9 h after nasal brushing, but the storage temperature modifies ciliary beating and needs to be controlled. [ABSTRACT FROM AUTHOR]

Background: Primary ciliary dyskinesia (PCD) is a type of ciliary dyskinesia that is usually caused by autosomal recessive inheritance and can manifest as recurrent respiratory infections, bronchiectasis, infertility, laterality defects, and chronic otolaryngological disease. Although ependymal cilia, which affect the flow of cerebrospinal fluid in the central nervous system, have much in common with respiratory cilia in terms of structure and function, hydrocephalus is rarely associated with PCD. Recently, variants of Forkhead box J1 (FOXJ1) have been found to cause PCD combined with hydrocephalus in a de novo, autosomal dominant inheritance pattern. Methods: We performed DNA extraction, whole‐exome sequencing (WES) analysis, and mutation analysis of FOXJ1 and analyzed the patient's clinical and genetic data. Results: The patient was a 4‐year‐old female exhibiting normal growth and development. At 3 years and 2 months of age, the patient experienced hand shaking and weakness in the lower limbs. Cardiac ultrasonography showed a right‐sided heart, and cranial magnetic resonance imaging showed obstructive hydrocephalus. The nasal nitric oxide level was 54 nL/min. WES indicated a de novo, heterozygous variant of FOXJ1, c.734–735 ins20. This variant was novel, not included in the Human Gene Mutation and Genome Aggregation Database, and likely pathogenic according to the American College of Medical Genetics and Genomics, causing earlier termination of amino acid translation. The patient underwent a neuroendoscopic third ventriculostomy after the diagnosis of obstructive hydrocephalus. Six months after the operation, the patient's motor deficits had improved. Conclusion: This is the first report of a de novo, autosomal dominant pattern of FOXJ1 causing PCD combined with hydrocephalus in China. The patient's clinical symptoms were similar to those previously reported. WES confirmed that a novel variant of FOXJ1 was the cause of the PCD combined with hydrocephalus, expanding the spectrum of the genotypes associated with this condition. Physicians should be aware of the correlation of hydrocephalus and PCD and test for FOXJ1 variants. [ABSTRACT FROM AUTHOR]

Dai Gong, Qiong Tang, Li-Juan Yan, Xiao-Min Ye, Yi-Can Yang, Li Zou, Qing Ji, Xiang-Lan Wen Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, Zhuzhou, Hunan, 412007, People’s Republic of ChinaCorrespondence: Xiang-Lan Wen, Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, No. 116 Changjiang Road, Tianyuan District, Zhuzhou, Hunan, 412007, People’s Republic of China, Tel/Fax +86 13873317331, Email wenxianglianwxl@126.comBackground: Primary ciliary dyskinesia (PCD) is a group of autosomal recessive genetic diseases caused by abnormal ciliary ultrastructure and/or function, resulting in reduced ciliary clearance function or other dysfunctions. PCD is one of the causes of recurrent respiratory tract infections in children. At present, there is no gold standard for diagnosis. In patients clinically suspected with PCD, a variety of examination methods are available to assist in diagnosis, such as high-speed video microscopic imaging to analyze ciliary movement patterns, transmission electron microscopy to observe ciliary ultrastructure, genetic testing, and detection of nitric oxide content in nasal expiratory air.Case Description: We present a case summary of the clinical data and treatment process of a child with PCD and short stature induced by Novel exon 1 of CCNO mutation (NM-021147.5) at c.323del, and the proband father and mother were heterozygous mutators, who was diagnosed and treated in the Pediatric Healthcare Department of our hospital. We treated the child with recombinant human growth hormone to increase the height, and the patient was also advised to improve nutrition, prevent and control infections, and encouraged sputum expectoration. We also recommended regular follow-up visits to the outpatient department, and to seek other symptomatic and supportive treatments as necessary.Conclusion: The height and nutritional status of the child improved after treatment. We also reviewed relevant literature to help clinicians improve their understanding of this disease.Keywords: gene test, primary ciliary dyskinesia, reduced ciliary clearance function, short stature