In the last decade, undiagnosed disease programs have emerged to address the significant number of individuals with suspected but undiagnosed rare genetic diseases. In our single-center study, we have launched a pilot program for pediatric patients with undiagnosed diseases in the second-largest university hospital in the Czech Republic. This study was prospectively conducted at the Department of Pediatrics at University Hospital Brno between 2020 and 2023. A total of 58 Czech patients with undiagnosed diseases were enrolled in the study. All children underwent singleton WES with targeted phenotype-driven analysis. We identified 28 variants, including 11 pathogenic, 13 likely pathogenic, and 4 VUS according to ACMG guidelines, as diagnostic of genetic diseases in 25 patients, resulting in an overall diagnostic yield of 43%. Eleven variants were novel and had not been previously reported in any public database. The overall clinical utility (actionability) enabling at least one type of change in the medical care of the patient was 76%, whereas the average number of clinical implications to individual patient care was two. Singleton WES facilitated the diagnostic process in the Czech undiagnosed pediatric population. We believe it is an effective approach to enable appropriate counseling, surveillance, and personalized clinical management.
- Klíčová slova
- Rare genetic diseases, Undiagnosed patients, Whole-exome sequencing,
- MeSH
- dítě MeSH
- genetické testování metody MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- nediagnostikované nemoci * genetika diagnóza epidemiologie MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- prospektivní studie MeSH
- sekvenování exomu * metody MeSH
- vzácné nemoci * genetika diagnóza MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Cardiac-urogenital syndrome [MIM # 618280] is a newly described very rare syndrome associated with pathogenic variants in the myelin regulatory factor (MYRF) gene that leads to loss of protein function. MYRF is a transcription factor previously associated only with the control of myelin-related gene expression. However, it is also highly expressed in other tissues and associated with various organ anomalies. The clinical picture is primarily dominated by complex congenital cardiac developmental defects, pulmonary hypoplasia, congenital diaphragmatic hernia, and urogenital malformations. CASE PRESENTATION: We present case reports of two siblings of unrelated parents in whom whole-exome sequencing was indicated due to familial occurrence of extensive developmental defects. A new, previously undescribed splicing pathogenic variant c.1388+2T>G in the MYRF gene has been identified in both patients. Both parents are unaffected, tested negative, and have another healthy daughter. The identical de novo event in siblings suggests gonadal mosaicism, which can mimic recessive inheritance. CONCLUSIONS: To our knowledge, this is the first published case of familial cardiac-urogenital syndrome indicating gonadal mosaicism.
- Klíčová slova
- MYRF gene, Scimitar syndrome, cardiac-urogenital syndrome, familiar occurrence, whole-exome sequencing,
- MeSH
- lidé MeSH
- mozaicismus * MeSH
- sekvenování exomu MeSH
- sourozenci * MeSH
- syndrom MeSH
- transkripční faktory genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- Myrf protein, human MeSH Prohlížeč
- transkripční faktory MeSH
Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) is a new disease in children and adolescents that occurs after often asymptomatic or mild COVID-19. It can be manifested by different clinical symptomatology and varying severity of disease based on multisystemic inflammation. The aim of this retrospective cohort trial was to describe the initial clinical presentation, diagnostics, therapy and clinical outcome of paediatric patients with a diagnosis of PIMS-TS admitted to one of the 3 PICUs. All paediatric patients who were admitted to the hospital with a diagnosis of paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) during the study period were enrolled in the study. A total of 180 patients were analysed. The most common symptoms upon admission were fever (81.6%, n = 147), rash (70.6%, n = 127), conjunctivitis (68.9%, n = 124) and abdominal pain (51.1%, n = 92). Acute respiratory failure occurred in 21.1% of patients (n = 38). Vasopressor support was used in 20.6% (n = 37) of cases. Overall, 96.7% of patients (n = 174) initially tested positive for SARS-CoV-2 IgG antibodies. Almost all patients received antibiotics during in-hospital stays. No patient died during the hospital stay or after 28 days of follow-up. Initial clinical presentation and organ system involvement of PIMS-TS including laboratory manifestations and treatment were identified in this trial. Early identification of PIMS-TS manifestation is essential for early treatment and proper management of patients.
- Klíčová slova
- COVID-19, PIMS-TS, SARS-CoV-2, paediatric patient, post-COVID syndrome,
- Publikační typ
- časopisecké články MeSH
The worldwide outbreak of the novel 2019 coronavirus disease (COVID-19) has led to recognition of a new immunopathological condition: paediatric inflammatory multisystem syndrome (PIMS-TS). The Czech Republic (CZ) suffered from one of the highest incidences of individuals who tested positive during pandemic waves. The aim of this study was to analyse epidemiological, clinical, and laboratory characteristics of all cases of paediatric inflammatory multisystem syndrome (PIMS-TS) in the Czech Republic (CZ) and their predictors of severe course. We performed a retrospective-prospective nationwide observational study based on patients hospitalised with PIMS-TS in CZ between 1 November 2020 and 31 May 2021. The anonymised data of patients were abstracted from medical record review. Using the inclusion criteria according to World Health Organization definition, 207 patients with PIMS-TS were enrolled in this study. The incidence of PIMS-TS out of all SARS-CoV-2-positive children was 0.9:1,000. The estimated delay between the occurrence of PIMS-TS and the COVID-19 pandemic wave was 3 weeks. The significant initial predictors of myocardial dysfunction included mainly cardiovascular signs (hypotension, oedema, oliguria/anuria, and prolonged capillary refill). During follow-up, most patients (98.8%) had normal cardiac function, with no residual findings. No fatal cases were reported.Conclusions: A 3-week interval in combination with incidence of COVID-19 could help increase pre-test probability of PIMS-TS during pandemic waves in the suspected cases. Although the parameters of the models do not allow one to completely divide patients into high and low risk groups, knowing the most important predictors surely could help clinical management.
- Klíčová slova
- COVID-19, Incidence, MIS-C, Myocardial dysfunction, Predictors, Severe outcome,
- MeSH
- COVID-19 * komplikace diagnóza epidemiologie MeSH
- dítě MeSH
- lidé MeSH
- pandemie MeSH
- prospektivní studie MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 * MeSH
- syndrom systémové zánětlivé reakce MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
Congenital disorders of glycosylation (CDG) are a rapidly growing family of genetic diseases with the phosphomannomutase 2 (PMM2)-CDG being the most common form of CDG. Most of these monogenic diseases are autosomal recessive and have multi-systemic manifestations, mainly psychomotor retardation, facial dysmorphisms, characteristic distribution of the fat pads, and variable coagulation abnormalities. The association of fetal hydrops with CDG has been reported, and pericardial effusion was also rarely observed in patients with PMM2-CDG. Here we describe an infant boy with PMM2-CDG. The diagnosis was suspected based on inverted nipples, fat pads, and combined coagulopathy. However, the primary symptom was progressive pericardial effusion leading to patient death at the age of 3 months. Screening for CDG performed by the use of isoelectric focusing of serum transferrin showed a typical PMM2-CDG pattern. Exome sequencing revealed one common pathogenic variant (c.691G > A/p.Val231Met) and one novel variant (c.447 + 3dupA) in the PMM2 gene. Both PMM2 variants were further confirmed by Sanger sequencing in both the proband and the parents' DNA. The novel variant was predicted to result in loss of donor splice site, and the analysis at mRNA level confirmed that it leads to exon five skipping (r.348_447del) and causes premature termination of translation to the protein (p.G117Kfs∗4), therefore is classified as likely pathogenic. Although there is no curative therapy for the PMM2-CDG at the moment, the other supportive care options are available to be offered. The definite diagnosis of PMM2-CDG can also assist in the process of genetic counseling, family planning, and preimplantation genetic diagnosis.
- Klíčová slova
- PMM2-CDG, novel splicing variant, pericardial effusion, phosphomannomutase 2, whole exome sequencing,
- Publikační typ
- časopisecké články MeSH
AIM: To evaluate the potential of the Support Vector Machine Regression model (SVM-RM) and Multilayer Neural Network Ensemble model (MLNN-EM) to improve the intraocular lens (IOL) power calculation for clinical workflow. BACKGROUND: Current IOL power calculation methods are limited in their accuracy with the possibility of decreased accuracy especially in eyes with an unusual ocular dimension. In case of an improperly calculated power of the IOL in cataract or refractive lens replacement surgery there is a risk of re-operation or further refractive correction. This may create potential complications and discomfort for the patient. METHODS: A dataset containing information about 2,194 eyes was obtained using data mining process from the Electronic Health Record (EHR) system database of the Gemini Eye Clinic. The dataset was optimized and split into the selection set (used in the design for models and training), and the verification set (used in the evaluation). The set of mean prediction errors (PEs) and the distribution of predicted refractive errors were evaluated for both models and clinical results (CR). RESULTS: Both models performed significantly better for the majority of the evaluated parameters compared with the CR. There was no significant difference between both evaluated models. In the ±0.50 D PE category both SVM-RM and MLNN-EM were slightly better than the Barrett Universal II formula, which is often presented as the most accurate calculation formula. CONCLUSION: In comparison to the current clinical method, both SVM-RM and MLNN-EM have achieved significantly better results in IOL calculations and therefore have a strong potential to improve clinical cataract refractive outcomes.
- Klíčová slova
- Artificial neural networks, Cataract, Cataract surgery, IOL calculation, Machine learning, Refractive results, Support vector machine,
- Publikační typ
- časopisecké články MeSH
The extent of research on children's speech in general and on disordered speech specifically is very limited. In this article, we describe the process of creating databases of children's speech and the possibilities for using such databases, which have been created by the LANNA research group in the Faculty of Electrical Engineering at Czech Technical University in Prague. These databases have been principally compiled for medical research but also for use in other areas, such as linguistics. Two databases were recorded: one for healthy children's speech (recorded in kindergarten and in the first level of elementary school) and the other for pathological speech of children with a Specific Language Impairment (recorded at a surgery of speech and language therapists and at the hospital). Both databases were sub-divided according to specific demands of medical research. Their utilization can be exoteric, specifically for linguistic research and pedagogical use as well as for studies of speech-signal processing.
- MeSH
- databáze faktografické * MeSH
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- srozumitelnost řeči * MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
At present, more and more researchers are applying tested mathematical-engineering methods into different domains of life. One of these areas is helping people with different forms of disabilities. Research in this area is focused on searching for the relation between clinical and electrophysiological symptoms of children with developmental dysphasia. Sleep EEG and speech analyses are the primary areas under discussion, while the finding of methods acceptable for improvement of the diagnosis and determination of therapeutic procedures is the research topic. It is possible to reduce fundamentally, or to cure optimally these disorders in advanced diagnosis. Therefore it is important to search for new methods and to combine what has been used separately till now.
- MeSH
- algoritmy MeSH
- databáze jako téma MeSH
- diagnóza počítačová přístrojové vybavení metody MeSH
- dítě MeSH
- elektroencefalografie MeSH
- epilepsie komplikace diagnóza MeSH
- lidé MeSH
- neuronové sítě (počítačové) * MeSH
- neuropsychologické testy MeSH
- počítačová simulace MeSH
- polysomnografie MeSH
- předškolní dítě MeSH
- referenční hodnoty MeSH
- shluková analýza MeSH
- studie případů a kontrol MeSH
- testy artikulace přístrojové vybavení metody MeSH
- výpočetní biologie MeSH
- vývojové poruchy řeči komplikace diagnóza patofyziologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
