No abstract available.
Ciliary Motility Disorders*

Kartagener's syndrome is an inherited condition characterized by triad of chronic paranasal sinusitis, situs inversus, and bronchiectasis. Since 1976, Afzelius found a lack of dynein arm in immotile spermatozoa by electron microscopy, numerous recent studies have focused on the ultrastructural defect in the cilia and reported that the variety type of ultrastructural defect in immotile cilia syndrome. We report a female patient who had the Kartagener's triad with rare multiple ultrastructural defect of cilia in one patient. The electron microscopic examination showed partial dynein arm defect, loss of radial spoke, microtubular transposition, and giant cilia.
Arm ; Bronchiectasis ; Cilia ; Ciliary Motility Disorders ; Dyneins ; Female ; Humans ; Kartagener Syndrome* ; Microscopy, Electron ; Sinusitis ; Situs Inversus ; Spermatozoa

Kartagener's syndrome, a congenital disease transmitted as an autosomal recessive illness with a prevalence of approximately 1:20,000 persons, is characterized by the triple association of situs inversus, bronchiectasis, and sinusitis. Affected persons have an incoordination of ciliary motility that leads to defective mucociliary transport, chronic bronchial infections. Kartagener's syndrome is a subset of the immotile cilia syndrome and therefore all patients with Kartagener's syndrome have immotile cilia with obvious ultrastructural defects in the ciliary axoneme. In the respiratory tract this inability presumably causes impaired clearance of mucus and inhaled particles and results in the chronic infections of the sinuses and bronchial trees that are characterized of the disease. The end-stage phenomenon in Kartagener's syndrome, respiratory or heart failure is a less common event and heart-lung transplantation is becoming an accepted therapy for patients with end-stage pulmonary disease in Kartagener's syndrome in many institutes. We report one case of Kartagener's syndrome in a 25-year-old young woman who was presented as respiratory and right heart failures, with review of literatures.
Academies and Institutes ; Adult ; Ataxia ; Axoneme ; Bronchiectasis ; Cilia ; Ciliary Motility Disorders ; Female ; Heart Failure ; Heart* ; Heart-Lung Transplantation ; Humans ; Kartagener Syndrome* ; Lung Diseases ; Mucociliary Clearance ; Mucus ; Prevalence ; Respiratory Insufficiency ; Respiratory System ; Sinusitis ; Situs Inversus ; Trees

Humans ; Consanguinity ; Exome Sequencing ; Mutation/genetics* ; Sequence Analysis, DNA ; Ciliary Motility Disorders ; Axonemal Dyneins/genetics*

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.
Humans ; Male ; Animals ; Mice ; Semen/metabolism* ; Dyneins/metabolism* ; Cilia/metabolism* ; Mutation ; Ciliary Motility Disorders/genetics*

Granular cell tumor(formerly named to be granular cell myoblastoma) was first described by Abrikossoff in 1926 and is a rare tumor thought to be of Schwann cell origin. It can occur at any soft tissue of the body, but most cases are found at the tongue, skin, breast and GI tract. Only 6% of them occur in respiratory system. We report two cases of asymptomatic granular cell tumor of the bronchus that were detected incidentally by bronchoscopy. One patient had aspiration pneumonia, the other had immotile cilia syndrome. The former patient was simply observed and bronchoscopic extirpation of the tumor was done in the latter patient.
Breast ; Bronchi* ; Bronchoscopy* ; Ciliary Motility Disorders ; Gastrointestinal Tract ; Granular Cell Tumor* ; Humans ; Pneumonia, Aspiration ; Respiratory System ; Skin ; Tongue

BACKGROUND: Several studies have suggested that impaired mucociliary clearance plays a role in the pathophysiology of bronchial asthma. Cough productive of mucoid sputum is common, and mucous plugs in the airways are frequently observed. These clinical features are in keeping with the histologic lesions of asthma, which involve primarily the epithelial and mucous-producing structures of the conducting airways. Some studies have shown that the mucociliary clearance is impaired in adult asthma, but it has not been studied in childhood asthma. The objectives of this study were to examine whether the mucociliary clearance is impaired in childhood asthma and to estimate the degree of impairment in comparison with that of immotile cilia syndrome. METHOD: Thirteen children with mild stable asthma and eight patients with immotile cilia syndrome completed this study. Ten healthy children were recruited as a normal control group. The whole-lung mucociliary clearance was measured by the radioaerosol technique. Aerosols, tin colloid particles tagged with the radionuclide technetium-99m(99mTc), were generated by means of nebulizer, and inhaled via a mouthpiece. The retention of radioactivity was measured at 30, 60, 90 and 120 minutes by gamma camera, and mucociliary clearance was calculated as percent retention at each time. RESULTS: 1) In each subject, the percent retention decreased variably with the lapse of time. 2) The percent retention of radionuclide decreased at each time in order of normal control, bronchial asthma and immotile cilia syndrome and the percent retention of immotile cilia syndrome was significantly higher than that of normal control at each time(p<0.05). 3) At two hours, the percent retention of bronchial asthma(65.0 1.8(SE)%) was significantly higher than that of the normal control(54.4 3.5%, p<0.05), and significantly lower than that of immotile cilia syndrome(73.3 +/- 1.4%, p<0.01). 4) When the percent retention was analyzed according to PC20 in the children with bronchial asthma, they had no relationship with each other. CONCLUSION: Mucociliary clearance in the children with bronchial asthma was significantly lower than normal control. This finding indicates that impaired mucociliary clearance operates in childhood asthma as well, and suggests that it may be one contributing factor in the pathogenesis of asthma. The degree of impairment, however, was not so severe as immotile cilia syndrome.
Adult ; Aerosols ; Asthma* ; Child* ; Cilia ; Ciliary Motility Disorders ; Colloids ; Cough ; Gamma Cameras ; Humans ; Mucociliary Clearance* ; Nebulizers and Vaporizers ; Radioactivity ; Sputum ; Tin

OBJECTIVE: To carry out genetic testing and prenatal diagnosis for a Chinese couple whom had conceived two fetuses featuring multiple malformations including polycystic kidney, polydactyly and encephalocele. METHODS: Following elective abortion, the fetus from the second pregnancy was subjected to whole exome sequencing. Suspected pathogenic variants were verified by Sanger sequencing of the fetus and its parents. RESULTS: The fetus was found to harbor compound heterozygous variants of the CEP290 gene, namely c.2743G>T (p.E915X) and c.2587-2A>T, which were respectively inherited from its father and mother. The same variants were not detected among 100 healthy controls nor reported previously. Bioinformatic analysis suggested both variants to be deleterious. The fetus was diagnosed with Meckel-Gruber syndrome. Prenatal diagnosis for the couple during their next pregnancy suggested that the fetus did not carry the above pathogenic variants. CONCLUSION The compound heterozygous variants of the CEP290 gene probably underlay the pathogenesis of Meckel-Gruber syndrome in the second fetus. Above finding has provided a basis for genetic counseling and prenatal diagnosis for the couple, and also enriched the mutational spectrum of the CEP290 gene.
China ; Ciliary Motility Disorders ; Encephalocele/genetics* ; Female ; Genetic Testing ; Humans ; Pedigree ; Polycystic Kidney Diseases/genetics* ; Pregnancy ; Prenatal Diagnosis ; Retinitis Pigmentosa

Objective: To evaluate the value of nasal nitric oxide (nNO) measurement as a diagnostic tool for Chinese patients with primary ciliary dyskinesia (PCD). Methods: This study is a retrospective study. The patients were recruited from those who were admitted to the respiratory Department of Respiratory Medicine, Children's Hospital of Fudan University from March 2018 to September 2022. Children with PCD were included as the PCD group, and children with situs inversus or ambiguus, cystic fibrosis (CF), bronchiectasis, chronic suppurative lung disease and asthma were included as the PCD symptom-similar group. Children who visited the Department of Child health Care and urology in the same hospital from December 2022 to January 2023 were selected as nNO normal control group. nNO was measured during plateau exhalation against resistance in three groups. Mann-Whitney U test was used to analyze the nNO data. The receiver operating characteristic of nNO value for the diagnosis of PCD was plotted and, the area under the curve and Youden index was calculated to find the best cut-off value. Results: nNO was measured in 40 patients with PCD group, 75 PCD symptom-similar group (including 23 cases of situs inversus or ambiguus, 8 cases of CF, 26 cases of bronchiectasis or chronic suppurative lung disease, 18 cases of asthma), and 55 nNO normal controls group. The age of the three groups was respectively 9.7 (6.7,13.4), 9.3 (7.0,13.0) and 9.9 (7.3,13.0) years old. nNO values were significantly lower in children with PCD than in PCD symptom-similar group and nNO normal controls (12 (9,19) vs. 182 (121,222), 209 (165,261) nl/min, U=143.00, 2.00, both P<0.001). In the PCD symptom-similar group, situs inversus or ambiguus, CF, bronchiectasis or chronic suppurative lung disease and asthma were significantly higher than children with PCD (185 (123,218), 97 (52, 132), 154 (31, 202), 266 (202,414) vs. 12 (9,19) nl/min,U=1.00, 9.00, 133.00, 0, all P<0.001). A cut-off value of 84 nl/min could provide the best sensitivity (0.98) and specificity (0.92) with an area under the curve of 0.97 (95%CI 0.95-1.00, P<0.001). Conclusions: nNO value can draw a distinction between patients with PCD and others. A cut-off value of 84 nl/min is recommended for children with PCD.
Humans ; Child ; Adolescent ; Nitric Oxide ; Retrospective Studies ; Cystic Fibrosis ; Bronchiectasis/diagnosis* ; Asthma/diagnosis* ; Hospitals, Pediatric ; Ciliary Motility Disorders/diagnosis*

OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with Meckel syndrome. METHODS: A pedigree with a history of three consecutive adverse pregnancies which presented at the First Affiliated Hospital of Zhengzhou University on August 31, 2017 was selected as the study subject. Clinical data of the pedigree were collected. High-throughput sequencing was carried out to screen for variants of ciliopathy-related genes in the third fetus following induced abortion, and candidate variant was verified by Sanger sequencing. RESULTS: The first pregnancy of the couple had ended as spontaneous abortion, whilst the fetus of the second pregnancy was suspected for having ciliopathy, though no genetic testing was carried out following elected abortion. The fetus of the third pregnancy was suspected for having ciliopathy, and high-throughput sequencing and Sanger sequencing had shown that the fetus had harbored compound heterozygous variants of the TMEM67 gene, including c.978+1G>A from the father and c.1288G>C (p.D430H) from the mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.978+1G>A was classified as a pathogenic variant (PVS1+PM2_Supporting+PP5), whilst the newly discovered c.1288G>C (p.D430H) was classified as a likely pathogenic variant (PM2_Supporting+PM3+PM5+PP3). CONCLUSION The c.978+1G>A and c.1288G>C (p.D430H) compound heterozygous variants of the TMEM67 gene probably underlay the three consecutive adverse pregnancies suspected for ciliopathy in this pedigree. The discovery of c.1288G>C (p.D430H) has also expanded the mutational spectrum of the TMEM67 gene.
Female ; Pregnancy ; Humans ; Pedigree ; East Asian People ; Ciliary Motility Disorders/genetics* ; Ciliopathies ; Abortion, Spontaneous ; Membrane Proteins/genetics*