A5014009839- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Hereditary Neurological Disorders
- Epilepsy research and treatment
- Neurological diseases and metabolism
- Genomic variations and chromosomal abnormalities
- Hearing, Cochlea, Tinnitus, Genetics
- Metabolism and Genetic Disorders
- Connexins and lens biology
- Toxin Mechanisms and Immunotoxins
- Cellular Mechanics and Interactions
- Pharmacological Effects and Toxicity Studies
- Skin and Cellular Biology Research
- Cellular transport and secretion
- Ion channel regulation and function
- Vestibular and auditory disorders
- Neurogenetic and Muscular Disorders Research
- RNA and protein synthesis mechanisms
- Ear Surgery and Otitis Media
- RNA modifications and cancer
- Genetic Neurodegenerative Diseases
Charles University
2017-2023
University Hospital in Motol
2018-2021
Abstract Recently, biallelic variants in the SORD gene were identified as causal for axonal hereditary neuropathy (HN). We ascertained spectrum and frequency of among a large cohort Czech patients with unknown cause HN. Exome sequencing data analysed (58 patients). The prevalent c.757del variant was tested fragment analysis (931 Sanger additional 70 done. PCR primers designed to amplify exclusion pseudogene SORD2P . Sequence differences between frequencies SNPs calculated. Eighteen from 16...
Neurodegenerative diseases of childhood present with progressive decline in cognitive, social, and motor function are frequently associated seizures different stages the disease. Here we report a patient severe neurodegeneration drug-resistant epilepsy unknown etiology from age 2 years.Using whole exome sequencing, found heterozygous missense de novo variant c.628G > A (p.Glu210Lys) UBTF gene. This was recently described as 11 patients similar characterized by developmental initially...
Epilepsy is a heterogeneous disease with broad phenotypic spectrum and diverse genotypes. A significant proportion of epilepsies has genetic aetiology. In our study, custom designed gene panel 112 genes known to be associated was used. total, one hundred fifty-one patients were tested (86 males / 65 females). cohort, the highest probability for identification cause seizure onset within first four weeks life (61.9% clarification rate) – about two times more than other groups. The level...
Introduction: Hearing loss (HL) is the most common sensory deficit in humans. HL an extremely heterogeneous condition presenting frequently as a nonsyndromic (NS) inherited autosomal recessive (AR) pattern, termed DFNB. Mutations affecting STRC gene cause DFNB type 16. Various types of mutations within have been reported from U.S. and German populations, but no information about relative contribution to NSHL-AR among Czech patients available. Methods Patients: Two hundred eighty-eight with...
Genetic variation occurring within conserved functional protein domains warrants special attention when examining DNA in the context of disease causation. Here we introduce a resource, freely available at www.prot2hg.com, that addresses question whether particular variant falls onto an annotated domain and directly translates chromosomal coordinates residues. The tool can perform multiple-site query simple way, whole dataset is for download as well incorporated into our own accessible...
Charcot-Marie-Tooth disease (CMT) is an umbrella term for inherited neuropathies affecting estimated one in 2,500 people. Over 120 CMT and related genes have been identified clinical gene panels often contain more than 100 genes. Such a large genomic space will invariantly yield variants of uncertain significance (VUS) nearly any person tested. This rise number VUS creates major challenges genetic counseling. Additionally, fewer individual known are being published as the academic merit...
Background Recently, a study providing insight into GABRB3 mutational spectrum was published (Møller et al 2017). The authors report considerable pleiotropy even for single mutations and were not able to identify any genotype–phenotype correlations. Methods proband (twin B) referred massively parallel sequencing of epilepsy-related gene panel because hypotonia neonatal seizures. revealed variant confirmed with Sanger in the twin A, both parents tested presence variant. Results We case...
Hearing loss is a genetically heterogeneous sensory defect, and the frequent causes are biallelic pathogenic variants in GJB2 gene. However, patients carrying only one heterozygous (monoallelic) variant represent long-lasting diagnostic problem. Interestingly, previous results showed that individuals with two times more prevalent among those hearing compared to normal-hearing individuals. This excess led us hypothesize there could be another region/DFNB1 locus. A hitherto undiscovered could,...
Variants in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been reported as being etiologically associated with early infantile epileptic encephalopathy type 2 (EIEE2). We report on two patients, a boy and girl, EIEE2 that present onset epilepsy, hypotonia, severe intellectual disability, poor eye contact.Massively parallel sequencing (MPS) of custom-designed panel for epilepsy containing 112 epilepsy-related genes was performed. Sanger used to confirm novel variants....
Variants in the ATL1 gene have been repeatedly described as second most frequent cause of hereditary spastic paraplegia (HSP), a motor neuron disease manifested by progressive lower limb spasticity and weakness. mainly patients with early onset HSP. We performed Sanger sequencing all coding exons adjacent intron regions ALT1 111 Czech pure form HSP additional Multiplex-Ligation Probe Analysis (MLPA) testing targeting 56 them. All except seven were previously tested SPAST negative results....
Abstract Focal cortical dysplasia (FCD) represents the most common cause of drug‐resistant epilepsy in adult and pediatric surgical series. However, genetic factors contributing to severe phenotypes FCD remain unknown. We present a patient with an exceptionally rapid development evolving super‐refractory status epilepticus. performed multiple clinical (serial EEG, MRI), biochemical (metabolic immunological screening), (WES from blood‐ brain‐derived DNA), histopathological investigations. The...
Abstract Schinzel–Giedion syndrome (SGS) is a very rare genetic disorder characterized by distinctive facial features, severe developmental delay, seizures, and skeletal abnormalities. Whole exome sequencing, Sanger correlation with already published variants cases allowed us to identify two different de novo mutations in the SETBP1 gene: NM_015559.2 (SETBP1): c.2601C > G (p.Ser867Arg) c. 2608 A (p.Gly870Ser) Czech patients presenting SGS features. Both are within exon 4 of SETBP1,...
Aims: Genomic studies play a major role in variant observations between and within populations identifying causal relationships genotypes phenotypes. Analyses using databases such as gnomAD can provide insight into the frequencies of alleles large populations. There have been reports that detail for several countries ethnic groups, but yet, there are no datasets Czech population. Patients Methods: Whole-exome sequencing (WES) data from 222 individuals Republic were analyzed by The Genome...