Type II congenital pulmonary airway malformation with primary ciliary dyskinesia in a 4-year-old child: A case report

A congenital pulmonary airway malformation (CPAM) combined with primary ciliary dyskinesia (PCD) has not been described in literature. Herein, we described the case of a 4-year-old boy who presented to us with recurrent productive cough and rhinorrhea for 2 years. High resolution computed tomography of the thorax revealed multiple, cystic, transparent shadows of different sizes near the posterior thoracic cavity in the lower lobe of the left lung. Thoracoscopic segmentectomy was carried out and histology confirmed a type II CPAM. Whole-exome sequencing revealed a compound heterozygous mutation (c.10568+1G>A, c.9484delG) in the DNAH11 gene associated with PCD that originated from the boy's mother and father, respectively. This report showed that when a child with CPAM presents with a productive cough and recurrent sinusitis, irrespective of situs inversus, PCD should be suspected. Genetic testing can aid in diagnosis.     

Pulmonary radioaerosol mucociliary clearance in diagnosis of primary ciliary dyskinesia

BACKGROUND: Methods relying on nasal ciliary motility for the diagnosis of primary ciliary dyskinesia (PCD) are often hampered by secondary ciliary dyskinesia. A functional test for pulmonary mucociliary clearance, which is not influenced by secondary nasal ciliary defects, would be a valuable tool in a PCD workup. METHODS: The diagnostic validity and repeatability of a pulmonary radioaerosol mucociliary clearance (PRMC) test for the diagnosis of PCD was assessed in the following three sequentially performed substudies: (1) a preliminary cross-sectional study of PRMC in patients with known PCD; (2) a prospective blinded trial of patients referred for suspicion of PCD; and (3) an implementation study of PRMC as a routine method used in a PCD workup. PRMC was studied after (99m)Tc-albumin colloid aerosol inhalation, and the results were compared to (1) the results of nasal ciliary motility studies, (2) ciliary ultrastructure, and (3) the final clinical diagnosis. The repeatability of PRMC was assessed in 14 patients. RESULTS: A total of 95 patients, 5 to 74 years of age, were included in the study (57 patients in whom PCD was diagnosed, 26 non-PCD patients, and 12 patients referred for PCD workup without a conclusive workup result). In substudy 1, 14 of 15 patients with known PCD showed impaired PRMC; the results were inconclusive in 1 patient. In substudy 2, among 59 patients referred for PCD workup PRMC test results, compared to nasal ciliary motility, showed a sensitivity of 88% and a specificity of 100%. In substudy 3, among 21 patients referred for PCD investigation who were included in a routine PCD workup after PRMC implementation, 71% of PRMC test results were in alignment with nasal ciliary motility. Repeatability of interpretation was seen in 13 of 14 cases. A conclusive PRMC after only one test was found in 81 of 95 patients (85%). CONCLUSION: PRMC is a noninvasive functional test for total tracheobronchial mucociliary clearance with a high sensitivity and specificity for PCD, a high rate of conclusive results after only one test and a further ability to separate PCD from focal pulmonary mucociliary defects.     

A case of paraneoplastic cerebellar degeneration associated with small cell lung cancer showing marked response to intravenous immunoglobulin

BACKGROUND: Paraneoplastic cerebellar degeneration (PCD), one of the paraneoplastic neurological syndromes (PNS), develops a subacute cerebellar dysfunction and its neurological prognosis is poor in most cases. Because it is considered to be immune-mediated, immunosuppressive therapy may be effective, but its past outcomes are not constant. CASE: A 59-year-old woman presented with deteriorating cerebellar manifestations such as ataxic gait, nausea, and dysarthria. Chest CT revealed a nodule in the upper lobe of the right lung, and small cell lung cancer was diagnosed by transbronchoscopic lung biopsy and sputum cytology. Although known antineuronal antibodies were not detected, no other causative diseases were recognized, so PCD associated with SCLC was diagnosed. The cerebellar manifestations improved remarkably with immediate intravenous immunoglobulin (IVIG) therapy. SCLC showed complete response (CR) after chemoradiotherapy, and the neurological symptoms have not worsened at present. CONCLUSION: Treatment with IVIG at the early stage may lead to the improvement of PCD and is worth attempting.     

Multifaceted analysis of Japanese cases of primary ciliary dyskinesia: Value of immunofluorescence for ciliary protein detection in patients with DNAH5 and DNAH11 mutations

Multifaceted analysis is recommended for the diagnosis of primary ciliary dyskinesia (PCD). A 31-year-old woman had situs inversus, bronchiectasis, family history of PCD, and compound heterozygous mutations in DNAH5. Her cilia were immotile. Defects in the outer dynein arms were revealed by transmission electron microscopy and loss of DNAH5 proteins in the entire length of axonemes using immunofluorescence (IF). A 17-year-old boy had bronchiectasis and heterozygous mutations in DNAH11. His cilia were motile with normal ultrastructure. The loss of DNAH11 proteins at the proximal region of cilia was revealed by IF. IF could be useful to support PCD diagnosis.     

Freeze-fracture analysis of the respiratory cilia from the bronchial mucosa of a patient with primary ciliary dyskinesia

Respiratory cilia of the bronchial mucosa from a 5-year-old boy with clinical evidence of classical Kartagener's syndrome (situs inversus, bronchiectasis and sinusitis) were first examined by means of transmission electron microscopy for identification of the axonemal defects described as typical for primary ciliary dyskinesia (PCD). Additional oscillography was performed on the cilia in vitro, which showed absence of a coordinated ciliary beat frequency. After clear classification of the case as PCD, a freeze-fracture examination of the respiratory cilia was performed, which revealed a higher density of intramembrane particles on the outer fracture face (E-face) than on the inner fracture face (P-face). The results were discussed with regard to probable pathogenetic aspects on PCD.     

原发性纤毛运动障碍1例及文献复习

目的 提高对原发性纤毛运动障碍(PCD)临床与病理特点的认识.方法 分析我院收治的1例PCD患者的临床资料及诊治经过,并复习相关文献.结果 患者临床表现为慢性咳嗽、咯痰、喘息;胸部CT表现为双肺弥漫的小结节改变并伴局部支气管扩张;经纤维支气管镜肺活检电镜病理表现为纤毛结构异常,动力臂缺失.其表现符合PCD.结论 PCD是由纤毛功能和(或)结构缺陷导致的一种常染色体隐性遗传病,容易误诊,其诊断依赖于纤毛超微结构检测.目前尚无标准治疗方案,以对症治疗为主.

Abstract：

Objective To improve the understanding of clinical and pathological characteristics of primary ciliary dyskinesia (PCD). Methods A case diagnosed with PCD was reported,and the related literatures were reviewed. Results The patient had cough,expectoration,and dyspnea. Chest CT scan showed diffuse nodules and local bronchieclasis. Transbronchial lung biopsy was done and transmission electron microscopy showed ciliary abnormalities and absence of dynein arms. Those findings were consistent with PCD. Conclusions PCD is an inherited disease characterised by functional and/or structural congenital abnormalities of cilia,and is often misdiagnosed. The diagnosis of PCD relies on the analysis of cilium ultrastructure. There is no specific therapy for PCD,and symptomatic treatment is recommended.     

原发性纤毛运动障碍1例及文献复习

目的 提高对原发性纤毛运动障碍(PCD)临床与病理特点的认识.方法 分析我院收治的1例PCD患者的临床资料及诊治经过,并复习相关文献.结果 患者临床表现为慢性咳嗽、咯痰、喘息;胸部CT表现为双肺弥漫的小结节改变并伴局部支气管扩张;经纤维支气管镜肺活检电镜病理表现为纤毛结构异常,动力臂缺失.其表现符合PCD.结论 PCD是由纤毛功能和(或)结构缺陷导致的一种常染色体隐性遗传病,容易误诊,其诊断依赖于纤毛超微结构检测.目前尚无标准治疗方案,以对症治疗为主.     

Modular coherence of protein dynamics in yeast cell polarity system

In this study, we investigated on a systems level how complex protein interactions underlying cell polarity in yeast determine the dynamic association of proteins with the polar cortical domain (PCD) where they localize and perform morphogenetic functions. We constructed a network of physical interactions among >100 proteins localized to the PCD. This network was further divided into five robust modules correlating with distinct subprocesses associated with cell polarity. Based on this reconstructed network, we proposed a simple model that approximates a PCD protein's molecular residence time as the sum of the characteristic time constants of the functional modules with which it interacts, weighted by the number of edges forming these interactions. Regression analyses showed excellent fitting of the model with experimentally measured residence times for a large subset of the PCD proteins. The model is able to predict residence times using small training sets. Our analysis also revealed a scaffold protein that imposes a local constraint of dynamics for certain interacting proteins.     

Paraneoplastic cerebellar degeneration (PCD) associated with squamous cell carcinoma of the lung

We report a case of a 71-year-old man who presented with cerebellar dysfunction. He was diagnosed as having squamous cell carcinoma of the lung (T2N3M0, Stage IIIB). No anti-onconeural antibodies were found in his serum. Cerebral spinal fluid (CSF) examination showed mild mononuclear pleocytosis alone. Magnetic resonance imaging (MRI) of the brain and spinal cord revealed no abnormalities. At autopsy, there was complete disappearance of Purkinje cells with reactive astrocytosis. These findings are compatible with paraneoplastic cerebellar degeneration (PCD). To our knowledge, no case of PCD has been reported previously in patients with squamous cell carcinoma of the lung.     

Predictors of outcome of percutaneous catheter drainage in patients with acute pancreatitis having acute fluid collection and development of a predictive model

BackgroundPercutaneous catheter drainage (PCD) is effective initial strategy in the step-up approach of management of acute pancreatitis (AP). The objective of this study was to identify factors associated with outcomes after PCD and develop a predictive model.Method and materialsIn a prospective observational study between July 2016 and Nov 2017, 101 consecutive AP patients were treated using a “step-up approach” in which PCD was used as the first step. We evaluated the association between success of PCD (survival without necrosectomy) and baseline parameters viz. etiology, demography, severity scores, C-reactive protein (CRP), and intra-abdominal pressure (IAP), morphologic characteristics on computed tomography (CT) [percentage of necrosis, CT severity index (CTSI), characteristics of collection prior to PCD (volume, site and solid component of the collection), PCD parameters (initial size, maximum size, number and duration of drainage) and factors after PCD insertion (fall in IAP, reduction in volume of collection).ResultsAmong 101 patients, 51 required PCD. The success rate of PCD was 66.66% (34/51). Four patients required additional surgical necrosectomy after PCD. Overall mortality was 29.4% (15/51). Multivariate analysis showed percentage of volume reduction of fluid collection (p = 0.016) and organ failure (OF) resolution (p = 0.023) after one week of PCD to be independent predictors of success of PCD. A predictive model based on these two factors resulted in area under curve (AUROC) of 0.915. Nomogram was developed with these two factors to predict the probability of success of PCD.ConclusionOrgan failure resolution and reduction in volume of collection after one week of PCD are significant predictors of successful PCD outcomes in patients with fluid collection following AP     

Analysis of premature centromere division (PCD) of the X chromosome in Alzheimer patients through the cell cycle

Cytogenetic analysis of the X chromosome in phytohaemagglutinin stimulated peripheral blood lymphocytes was evaluated in 12 sporadic Alzheimer disease (AD) patients and in 11 healthy subjects. For chromosome analysis two methods were used: (1) standard analysis of G-banded metaphase chromosomes and; (2) fluorescent in situ hybridization (FISH) for the detection of the X chromosome centromeric region in interphase nuclei. Cytogenetic analysis revealed that the X chromosome expresses premature centromere division (PCD) in AD females in 10.53% of metaphase cells and in 15.22% of interphase nuclei. In AD men the percentages were 3.98 and 6.06%, respectively. X chromosome PCD in the female control group showed a percentage of 7.46% in metaphase cells and 9.35% in interphase nuclei and in male controls the percentages were 2.84% in metaphases and 5.54% in interphase nuclei. The results of FISH analysis showed that PCD could occur much earlier than metaphase of mitosis, i.e. in interphase of the cell cycle, immediately after replication. The FISH method can be used for PCD verification in all phases of the cell cycle in various disorders including AD.     

Seminal plasma induces programmed cell death in cultured peripheral blood mononuclear cells

Immunosuppressive properties of seminal plasma inhibit the recovery of infectious HIV from semen, and led to the view early in the pandemic that semen HIV was transmitted principally by infected semen cells. More recent studies have revealed significant titers of HIV RNA in seminal plasma, however, even from men receiving successful antiviral therapy. Thus, studies of infectious HIV in seminal plasma are important to understanding sexual transmission and response to therapy. The present studies were undertaken to determine whether seminal plasma immunosuppression is mediated by the induction of programmed cell death (PCD). Peripheral blood mononuclear cells (PBMCs) were cultured without or with phytohemagglutinin and seminal plasma from normal donors, or men postvasectomy, or seminal vesicle protein collected at surgery. PBMC survival was measured at 3, 6, and 18 hr of culture; cells were examined for evidence of PCD by uptake of the fluorescent dye YO-PRO, and for fragmented nuclear DNA by the TUNEL assay. Approximately 90% of PBMCs cultured with seminal plasma from intact or vasectomized men were lost during 18 hr of culture; seminal vesicle protein did not induce cell loss. PCD assays were positive for PBMCs exposed to the seminal plasma, and negative for PBMCs cultured with seminal vesicle protein. Serum was not required for PCD induction. A 3-hr pulse with seminal plasma was sufficient to initiate PCD. These findings indicate that PCD induction accounts for the cytotoxic properties of semen, that the PCD is not the result of semen amine oxidases, and either that substances produced by seminal vesicles only at ejaculation, or by the prostate, are responsible for PCD induction.     

Significance of chronic bifascicular block without apparent organic heart disease.

Eighty-six of 452 patients (19%) with chronic bifascicular block were found to have no clinically apparent associated organic heart disease (OHD) and were defined as having primary conduction disease (PCD). Comparison of patients with PCD and OHD revealed a significantly lower incidence of the following clinical variables in the PCD patients (p less than 0.001): exertional angina, dyspnea, congestive heart failure, cardiomegaly, functional class I (all by study design), left bundle branch block and premature ventricular contractions. Both mean AH and HV intervals were significantly shorter in patients with PCD (p less than 0.01). The incidence of HV prolongation was 21% in PCD and 41% in OHD patients (p less than 0.001). All patients were prospectively followed for 21-2998 days with a mean +/- SEM of 1209 +/- 66 days for PCD and 1172 +/- 36 days for OHD. Atrioventricular (AV) block developed in three patients from the PCD group and 26 from the OHD group (NS), with spontaneous block occurring in one (1%) PCD patient and 19 (5%) OHD patients (p less than 0.05). Annual mortality due to sudden death as well as total cardiovascular mortality (including sudden death) for the 5-year follow-up was significantly lower in patients with PCD. Patients with PCD have significantly lower incidence of electrophysiologic abnormalities and subsequent spontaneous AV block as well as cardiovascular and sudden death mortality. The diagnosis of PCD based on clinical criteria probably underestimates the presence of underlying OHD, as suggested by a small but definite risk of cardiovascular mortality.     

Plasmacytic differentiation in MALT lymphomas following treatment with rituximab

Mucosa-associated lymphoid tissue (MALT) lymphomas are B cell neoplasms which commonly affect the gastrointestinal (GI) tract. Gastrointestinal MALT lymphomas rarely show plasmacytic differentiation (PCD), and limited data on the potential influence of the anti-CD20 antibody rituximab (R) on PCD exist in the current literature. We have retrospectively analyzed patients with GI MALT lymphomas treated with R-containing regimens because restaging is routinely performed by repeated biopsies with pathohistological response assessment. Twenty-one patients with GI MALT lymphoma were identified to have undergone R-containing therapy. In 19 patients, the lymphoma originated in the stomach, while the colon was the primarily affected organ in two cases. Four patients received R monotherapy and 17 combinations of R with various chemotherapeutic agents. Only two patients with gastric MALT lymphoma had PCD before initiation of therapy. In 7 of 19 patients (37%) without PCD at diagnosis, restaging revealed PCD after or while on treatment with R-containing regimens. Out of these seven patients, only one patient had a complete response as opposed to 10/12 without PCD. These data suggest that R or R-containing treatment regimens may not optimally eradicate the plasma cell component and thus lead to PCD in patients with GI MALT lymphoma. In view of this, rebiopsy and histological re-assessment appear mandatory in patients failing/relapsing after R-containing regimens.     

Identification of immunosuppressant-induced apoptosis in a murine B-cell line and its prevention by bcl-x but not bcl-2.

Cyclosporin A, FK-506, and rapamycin are immunosuppressants often used as pharmacological probes to study lymphocyte activation and physiological cell death (PCD). Because cyclosporin A and FK-506 are known to prevent PCD in T-cell hybridomas and thymocytes, we used these reagents, as well as rapamycin, to determine whether they alter the pathway leading to apoptosis in murine WEHI-231 cells following surface IgM cross-linking. We observed that the immunosuppressants themselves induced PCD in WEHI-231 cells, but only in sublines susceptible to anti-IgM-mediated apoptosis. PCD was preceded by growth arrest and characterized by the DNA fragmentation pattern typical of apoptosis. In B-cell lines resistant to anti-immunoglobulin- and immunosuppressant-induced PCD, cyclosporin A, FK-506, and rapamycin caused growth arrest. PCD was also induced by inhibitors of protein synthesis in WEHI-231 cells but not in the mature B-cell line BAL-17. Immunosuppressant-induced and protein synthesis inhibitor-induced PCD, but not growth arrest, could be prevented by the overexpression of bcl-xL, while transfection with bcl-2 did not affect PCD or cell cycle arrest. These results suggest that bcl-2 and bcl-xL may control partially independent systems to inhibit PCD in lymphoid cells and that PCD in B and T cells may be differentially regulated.     

Primary carnitine deficiency and pivalic acid exposure causing encephalopathy and fatal cardiac events

Background

Several episodes of sudden death among young Faroese individuals have been associated with primary carnitine deficiency (PCD). Patients suffering from PCD have low carnitine levels and can present with metabolic and/or cardiac complications. Pivalic acid exposure decreases carnitine levels. The purpose of this study was to investigate and describe the association and pathophysiology of exposure to antibiotics containing pivalic acid and severe neurological and cardiac complications in six identified subjects suffering from PCD.

Methods and materials

Six cases of PCD were identified and studied through medical records and family interview. Stored biomaterial was analyzed for mutations causing PCD.

Results

Five patients (two children, three adults) died suddenly while one adult patient survived sudden cardiac arrest. Lethal cardiac arrhythmia was documented in five patients, while one patient was not monitored at time of death, but had signs of cardiac arrhythmia a few days earlier. All patients suffered encephalopathy before cardiac arrhythmia. Autopsy showed severe hepatic steatosis and signs of cerebral edema in four out of five. One subject had a dilated heart. All patients were homozygous for the c.95A>G (p.N32S) mutation in SLC22A5 causing PCD. All patients had been treated with antibiotics containing pivalic acid prior to the episode.

Conclusion

Exposure to antibiotics containing pivalic acid was associated with encephalopathy and progression to lethal cardiac arrhythmia in patients suffering from PCD.     

Post-Cholecystectomy Diarrhea: Evidence of Bile Acid Malabsorption Assessed by SeHCAT Test

Although bile acid malabsorption (BAM) in post-cholecystectomy diarrhea (PCD) is a well-known clinical condition, its true etiopathogenetic role is not entirely clear. The SeHCAT (23-selena-25-homotaurocholic acid) test, a simple and reliable BAM test, was performed in 33 cholecystectomized patients, 26 with chronic diarrhea. The test revealed a marked degree of BAM in 25/26 cases. Cholestyramine in doses of 2-12 g/day was effective in 23/25, ineffective in two, and was not tolerated in one patient. When treatment was suspended, diarrhea recurred in nine, whereas bowel habit remained regular in 60%, with brief sporadic episodes of diarrhea in the other cases. The SeHCAT test was repeated in 11 cases after cholestyramine treatment interruption, and revealed the normalization of parameters in two patients and an improvement in three. We conclude that BAM is an important etiopathogenetic factor in PCD that responds favorably to cholestyramine. In 60% of the cases, it resolved diarrhea definitively, although without eliminating BAM in all cases: this suggests that existence of other factors associated with BAM. The SeHCAT test is essential for a differential diagnosis between PCD and the irritable bowel syndrome.     

Timing of surgical intervention in patients of infected necrotizing pancreatitis not responding to percutaneous catheter drainage

BackgroundThe timing of surgery in patients not responding to percutaneous catheter drainage (PCD) in infected pancreatic necrosis remains challenging.Materials and methodsA randomized controlled trial was designed to establish the optimal timings of surgery following PCD in patients with infected pancreatic necrosis (IPN). Patients who did not improve by day 10 after PCD insertion were included in the present study and were randomized to group A (step-up approach as a bridge to surgery) or group B (step-up approach with intention to avoid surgery). Weekly inflammatory and nutritional markers were monitored in both groups (clinical trials. gov identifier NCT-01527084).ResultsFrom July 2011 to December 2012, 40 patients underwent treatment with PCD. The first 8 patients were randomized into two groups. The trial was stopped prematurely because of difficulty in accrual and poor progress. All subsequent patients were managed with step-up approach with the intention to avoid surgery. Of 35 patients, 24 patients were managed by PCD alone while 11 patients required surgery. In patients who did not require surgery; levels of serum high sensitivity C-reactive protein (hsCRP), interleukin-6(IL6) and prealbumin showed a falling trend. This group also had higher baseline albumin and higher albumin at 4 weeks.ConclusionDuring the present study, randomization into surgery at a predetermined time in step-up approach was discontinued due to poor progress. Step-up approach with the intention to avoid surgery led to a success rate of 68.5%. The present study failed to predict the optimal timing of surgery after PCD. Patients who needed surgery were sicker at the time of admission, had higher incidence of organ failure, and spent more time in the ICU compared to patients who did not need surgery. In future, inflammatory and nutritional markers may be useful to identify patients who are unlikely to respond to PCD and may help determine the timing of surgery.     

Clinical and ultrastructural study on primary ciliary dyskinesia

We evaluated laboratory and radiological findings and examined tracheobronchial cilia by transmission electron microscopy in 9 patients with primary ciliary dyskinesia (PCD), in order to elucidate the clinical pictures of PCD and the relationship between PCD and diffuse panbronchiolitis (DPB) which was proposed as a new disease entity in Japan in 1969. The clinical pictures of our PCD patients were almost the same as that already described in several articles in Europe and North America; early onset of respiratory symptoms, high incidence of chronic sinusitis and otitis media exudative as well as infertility, continuous infections in the lower respiratory tracts (Hemophilus influenzae, Pseudomonas aeruginosa etc.). Tracheobronchial cilia obtained by brushing technique were immotile (6 out of 8 patients) or dyskinetic (2 out of 8 patients). Ultrastructural study of cilia revealed the lack of dynein arms in all patients: the lack of both outer and inner arms (4 patients), the lack of outer arms (2 patients), the lack of inner arms (2 patients). Chest X-ray films revealed situs inversus in six out of nine patients. According to the radiological findings (chest X-ray film, CT-scan, bronchogram), the patients were divided into three groups; I: localized bronchiectasis (5 patients), II: diffuse micronodular lesions without definite bronchiectasis (3 patients), III: diffuse micronodular lesions with bronchiectasis (1 patient). Two patients of the second group satisfied the clinical diagnostic criteria for DPB (Chest 83:63, 1983). In conclusion, PCD can cause a variety of respiratory tract lesions such as bronchiectasis, DPB and other types of peripheral airway disorders.     

Analysis of the diagnosis of Japanese patients with primary ciliary dyskinesia using a conditional reprogramming culture

BackgroundPrimary ciliary dyskinesia (PCD) is diagnosed through multiple methods, including transmission electron microscopy (TEM), a high-speed video microscopy analysis (HSVA), immunofluorescence (IF), and genetic testing. A primary cell culture has been recommended to avoid the misdiagnosis of secondary ciliary dyskinesia derived from infection or inflammation and improve diagnostic accuracy. However, primary cells fail to differentiate into ciliated cells through repeated passages. The conditional reprogramming culture (CRC) method, a combination of a Rho-kinase inhibitor and fibroblast feeder cells, has been applied to cystic fibrosis. The goal of this study was to evaluate the value of CRC in diagnosing PCD in Japanese patients.MethodsEleven patients clinically suspected of having PCD were included. Airway epithelial cells were obtained from an endobronchial forceps biopsy and cultured at the air-liquid interface (ALI) combined with CRC. Ciliary movement, ultrastructure, and mutated ciliary protein evaluation were performed using HSVA, TEM, and IF, respectively. Genetic testing was performed on some patients.ResultsCRC yielded dense and well-differentiated ciliated cells with a high success rate (～90%). In patients with PCD, the ciliary ultrastructure phenotype (outer dynein arm defects or normal ultrastructure) and IF findings (absence of the mutated ciliary protein) were confirmed after CRC. In DNAH11-mutant cases with normal ultrastructure by TEM, the HSVA revealed stiff and hyperfrequent ciliary beating with low bending capacity in CRC-expanded cells, thereby supporting the diagnosis.ConclusionsCRC could be a potential tool for improving diagnostic accuracy and contributing to future clinical and basic research in PCD.