BACKGROUND: Primary ciliary dyskinesia (PCD) represents a group of rare hereditary disorders characterised by deficient ciliary airway clearance that can be associated with laterality defects. We aimed to describe the underlying gene defects, geographical differences in genotypes and their relationship to diagnostic findings and clinical phenotypes. METHODS: Genetic variants and clinical findings (age, sex, body mass index, laterality defects, forced expiratory volume in 1 s (FEV1)) were collected from 19 countries using the European Reference Network's ERN-LUNG international PCD Registry. Genetic data were evaluated according to American College of Medical Genetics and Genomics guidelines. We assessed regional distribution of implicated genes and genetic variants as well as genotype correlations with laterality defects and FEV1. RESULTS: The study included 1236 individuals carrying 908 distinct pathogenic DNA variants in 46 PCD genes. We found considerable variation in the distribution of PCD genotypes across countries due to the presence of distinct founder variants. The prevalence of PCD genotypes associated with pathognomonic ultrastructural defects (mean 72%, range 47-100%) and laterality defects (mean 42%, range 28-69%) varied widely among countries. The prevalence of laterality defects was significantly lower in PCD individuals without pathognomonic ciliary ultrastructure defects (18%). The PCD cohort had a reduced median FEV1 z-score (-1.66). Median FEV1 z-scores were significantly lower in CCNO (-3.26), CCDC39 (-2.49) and CCDC40 (-2.96) variant groups, while the FEV1 z-score reductions were significantly milder in DNAH11 (-0.83) and ODAD1 (-0.85) variant groups compared to the whole PCD cohort. CONCLUSION: This unprecedented multinational dataset of DNA variants and information on their distribution across countries facilitates interpretation of the genetic epidemiology of PCD and indicates that the genetic variant can predict diagnostic and phenotypic features such as the course of lung function.

• MeSH
• axonemální dyneiny genetika   MeSH
• cytoskeletální proteiny MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp * MeSH
• genetická variace MeSH
• genetické asociační studie * MeSH
• genotyp * MeSH
• Kartagenerův syndrom genetika   patofyziologie   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace MeSH
• předškolní dítě MeSH
• proteiny MeSH
• registrace MeSH
• senioři MeSH
• usilovný výdechový objem MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• axonemální dyneiny MeSH
• CCDC39 protein, human MeSH Prohlížeč
• CCDC40 protein, human MeSH Prohlížeč
• cytoskeletální proteiny MeSH
• DNAH11 protein, human MeSH Prohlížeč
• proteiny MeSH

• Klíčová slova
• infant, infant lung function, primary ciliary dyskinesia, ventilation inhomogeneity,
• MeSH
• cilie MeSH
• Kartagenerův syndrom * komplikace   MeSH
• kojenec MeSH
• lidé MeSH
• plíce MeSH
• poruchy ciliární motility * komplikace   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• Publikační typ
• dopisy MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no "gold standard" reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia.

• MeSH
• cilie patologie   ultrastruktura   MeSH
• delfská metoda MeSH
• diferenciální diagnóza MeSH
• fluorescenční protilátková technika MeSH
• genetické testování MeSH
• Kartagenerův syndrom diagnóza   genetika   MeSH
• lidé MeSH
• oxid dusnatý analýza   MeSH
• přehledová literatura jako téma MeSH
• společnosti lékařské MeSH
• transmisní elektronová mikroskopie MeSH
• videomikroskopie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• směrnice pro lékařskou praxi MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• oxid dusnatý MeSH

BACKGROUND: Primary ciliary dyskinesia (PCD) is a multigenic autosomal recessive condition affecting respiratory tract and other organs where ciliary motility is required. The extent of its genetic heterogeneity is remarkable. The aim of the study was to develop a cost-effective pipeline for genetic diagnostics using a combination of Sanger and next generation sequencing (NGS). MATERIALS AND METHODS: Data and samples of 33 families with 38 affected subjects with PCD diagnosed in childhood were collected over the territory of the Czech Republic. A panel of 18 PCD causative or candidate genes was implemented into an Illumina TruSeq Custom Amplicon NGS assay, and three ancestral mutations in SPAG1 were screened by conventional Sanger sequencing, which was also used for the confirmation of the NGS results and for the analysis of familial segregation. RESULTS: The causative gene was DNAH5 in 11/33 (33%) probands, SPAG1 in 8/33 (24%), and DNAI1, CCDC40, LRRC6 in one family each. If the high proportion of subjects with bi-allelic ancestral mutations in SPAG1 is corroborated in other Caucasian populations, a simple Sanger sequencing test for these three mutations may serve as an effective pre-screening step, being followed by an NGS panel for other, much larger, PCD genes. CONCLUSIONS: We present a combination of Sanger sequencing with an NGS panel for known and candidate PCD genes, implemented in a moderate-size national collection of patients. This strategy has proven to be cost-effective, rapid and reliable, and was able to detect the causative gene in two thirds of our PCD patients.

• Klíčová slova
• SPAG1 gene, next generation sequencing, targeted panel,
• MeSH
• alely MeSH
• antigeny povrchové genetika   MeSH
• dítě MeSH
• Kartagenerův syndrom diagnóza   genetika   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mutace * MeSH
• předškolní dítě MeSH
• proteiny vázající GTP genetika   MeSH
• vysoce účinné nukleotidové sekvenování * MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antigeny povrchové MeSH
• proteiny vázající GTP MeSH
• SPAG1 protein, human MeSH Prohlížeč

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare genetically heterogenous condition. Mutations in DNAH5 or DNAI1 genes can be found in about a third of the patients with PCD. Increased occurrence of mutations was described in several exons of these long genes. The objective of the study was to test the sensitivity of sequencing of selected 13 exons (as compared to costly sequencing of all 100 exons of the two genes), and to determine the prevalence of the DNAH5 or DNAI1 mutations in the Czech PCD database. METHODS: The Czech national PCD database has identified 31 pediatric patients, diagnosed based on clinical findings and tests on the ciliated epithelium. Twenty-seven patients from 24 families agreed on genetic testing. In the first step, direct sequencing of selected 13 exons (9 of DNAH5 and 4 of DNAI1) was performed, and then we compared its effectiveness in detecting at least one mutation with results of sequencing all 100 exons of the two genes. RESULTS: The sequencing of all exons identified compound heterozygosity for PCD mutations in nine patients from eight families (DNAH5 in eight and DNAI1 in one patient), and heterozygozity for a DNAH5 mutation of uncertain functional significance in one additional patient. The first step of selected exon sequencing detected a mutation in five out of these eight families, its actual sensitivity being 62.5%, with a high predictive value. The phenotypic and clinical characteristics of all the paediatric patients with PCD are shown. CONCLUSIONS: Selected exon sequencing detects at least one mutated allele in over a half of our patients who have PCD due to DNAH5 or DNAI1 mutations. To lower the costs of the genetic testing, targeted step-wise genetic testing may be a reasonable approach to detect mutations in PCD patients, especially if their phenotype is taken into account.

• MeSH
• alely MeSH
• axonemální dyneiny genetika   MeSH
• databáze faktografické MeSH
• dítě MeSH
• dospělí MeSH
• exony genetika   MeSH
• genetické testování ekonomika   MeSH
• genotyp MeSH
• Kartagenerův syndrom diagnóza   genetika   MeSH
• kohortové studie MeSH
• kontrola nákladů MeSH
• lidé MeSH
• mutace MeSH
• polymerázová řetězová reakce MeSH
• sekvenční analýza DNA MeSH
• senzitivita a specificita MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• axonemální dyneiny MeSH
• DNAH5 protein, human MeSH Prohlížeč
• DNAI1 protein, human MeSH Prohlížeč

Abnormal localization of the heart in the chest is a rare congenital developmental disorder (1,10). Even if the heart is in these instances normally developed, its abnormal position leads in case of its affection by disease to diagnostic and therapeutic difficulties, in particular when an invasive procedure must be used. With regard to the entirely different position of individual cardiac departments it is necessary to differentiate carefully between dextrocardia and dextroversion (15). Dextroposition is only a marginal problem. A very satisfactory diagnostic method in these anomalies is the ECG tracing, where we encounter quite typical pictures. Dextrocardia and dextroversion are characterized by a similar mirror image reversed tracing in the leads from the extremities. It differs, however, fundamentally in the chest lead tracings. In dextrocardia during tracing of standard thoracic leads we follow the predominant negative QRS complex in all leads; when including the dextrolateral thoracic leads the curve "becomes normal". In dextroversion, with regard to the anterior position of the left ventricle the dominating finding is a high R wave in all leads from the left and right side of the chest.

• MeSH
• dextrokardie diagnóza   MeSH
• diferenciální diagnóza MeSH
• elektrokardiografie * MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

In 25 children with damaged mucociliary function of the nasal mucosa the authors used local ATP treatment. It was found that ATP solution applied to the nasal mucosa improves mucociliary function and reduces the transport time to normal; in acute, relapsing and allergic rhinosinusitis, in Kartagener's syndrome it improves partially the function of cilia, while transport remains prolonged. It seems that local application of ATP in drops may have a favourable effect on rhinosinusitis and prevent relapses.

• MeSH
• adenosintrifosfát terapeutické užití   MeSH
• akutní nemoc MeSH
• dítě MeSH
• Kartagenerův syndrom farmakoterapie   patofyziologie   MeSH
• lidé MeSH
• mukociliární clearance účinky léků   MeSH
• respirační alergie farmakoterapie   MeSH
• sinusitida farmakoterapie   patofyziologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• adenosintrifosfát MeSH

• MeSH
• cilie fyziologie   MeSH
• dospělí MeSH
• Kartagenerův syndrom * patologie   patofyziologie   MeSH
• lidé MeSH
• spermie ultrastruktura   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH

• MeSH
• dextrokardie klasifikace   diagnóza   MeSH
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• terminologie jako téma MeSH
• vrozené srdeční vady diagnóza   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH

• MeSH
• bronchy patologie   ultrastruktura   MeSH
• cilie ultrastruktura   MeSH
• dítě MeSH
• epitel patologie   ultrastruktura   MeSH
• Kartagenerův syndrom patologie   MeSH
• lidé MeSH
• mladiství MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH