Zdeněk Sedláček
A5001533302- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Cancer-related Molecular Pathways
- Prenatal Screening and Diagnostics
- Genetic Neurodegenerative Diseases
- Epigenetics and DNA Methylation
- Chromosomal and Genetic Variations
- Autism Spectrum Disorder Research
- Hedgehog Signaling Pathway Studies
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Nutrition, Genetics, and Disease
- Ubiquitin and proteasome pathways
- Genetic Syndromes and Imprinting
- CRISPR and Genetic Engineering
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Congenital Ear and Nasal Anomalies
- Chromatin Remodeling and Cancer
- Cellular transport and secretion
- DNA Repair Mechanisms
- Congenital heart defects research
- Neuroblastoma Research and Treatments
- Muscle Physiology and Disorders
Charles University
2016-2025
University Hospital in Motol
1992-2024
Amsterdam University of Applied Sciences
2014
Institute of Human Genetics
2014
Columbia College - Missouri
2014
University of Oxford
2013
Medical Genetics Center
2012
Czech Academy of Sciences, Institute of Molecular Genetics
2011
Institute for Postgraduate Medical Education
2005
Czech Academy of Sciences, Institute of Animal Physiology and Genetics
2002
Most genes associated with neurodevelopmental disorders (NDDs) were identified an excess of de novo mutations (DNMs) but the significance in case-control mutation burden analysis is unestablished. Here, we sequence 63 16,294 NDD cases and additional 62 6,211 cases. By combining these published data, assess a total 125 over 16,000 compare to nonpsychiatric controls from ExAC. We identify 48 (25 newly reported) showing significant ultra-rare (MAF < 0.01%) gene-disruptive (FDR 5%), six which...
Abstract Myotonic dystrophy type 1 is caused by the expansion of a CTG repeat in 3′ UTR DMPK gene. A length exceeding 50 triplets pathogenic. Intermediate alleles with 35–49 are not disease‐causing but show instability intergenerational transmissions. We report on identification multiple patients different patterns CCG and CTC interruptions tract that display unique instability. In bearing interrupted expanded alleles, location changed dramatically between generations repeats tended to...
A transition from fetal hemoglobin (HbF) to adult (HbA) normally occurs within a few months after birth. Increased production of HbF this period infancy ameliorates clinical symptoms the major disorders β-hemoglobin: β-thalassemia and sickle cell disease. The transcription factor BCL11A silences has been an attractive therapeutic target for increasing levels; however, it is not clear what extent inhibits or mediates other developmental functions in humans. Here, we identified characterized 3...
Through the agnostic screening of patients with uncharacterised disease phenotypes for an upregulation type I interferon (IFN) signalling, we identified a cohort individuals heterozygous mutations in PTPN1, encoding protein-tyrosine phosphatase 1B (PTP1B). We aimed to describe clinical phenotype and molecular cellular pathology this new disease. In case series, collected neuroradiological data through collaboration paediatric neurology genetics colleagues across Europe (Czechia, France,...
Journal Article A strategy for the selection of transcribed sequences in Xq28 region Get access Bernhard Korn, Korn Search other works by this author on: Oxford Academic PubMed Google Scholar Zdenek Sedlacek, Sedlacek Antonella Manca, Manca Petra Kioschis, Kioschis David Konecki, Konecki Hans Lehrach, Lehrach 1Imperial Cancer Research Fund, 44 Uncoln's Inn FieldsLondon WC2A 3PX, UK Annemarie Poustka * *To whom correspondence should be addressed Human Molecular Genetics, Volume 1, Issue 4,...
CTG repeat expansions in DMPK cause myotonic dystrophy (DM1) with a continuum of severity and ages onset. Congenital DM1 (CDM1), the most severe form, presents distinct clinical features, large expansions, almost exclusive maternal transmission. The correlation between CDM1 expansion size is not absolute, suggesting contributions other factors. We determined CpG methylation flanking 79 blood samples from 20 CDM1-affected individuals; 21, 27, 11 individuals but (henceforth non-CDM1) maternal,...
Both gain- and loss-of-function mutations have recently implicated HCFC1 in neurodevelopmental disorders. Here, we extend our previous over-expression studies by employing short hairpin RNA to reduce the expression of Hcfc1 embryonic neural cells. We show that contrast over-expression, loss favoured proliferation progenitor cells at expense differentiation promoted axonal growth post-mitotic neurons. To further support involvement neurological disorders, report two novel missense variants...
Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 PRPF19, encoding spliceosome subunits neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo missense (including seven recurrent 30 individuals) six PRPF19 variants. Eight dysregulated model substrate....
Abstract Neurodevelopmental proteasomopathies represent a distinctive category of neurodevelopmental disorders (NDD) characterized by genetic variations within the 26S proteasome, protein complex governing eukaryotic cellular homeostasis. In our comprehensive study, we identified 23 unique variants in PSMC5 , which encodes AAA-ATPase proteasome subunit PSMC5/Rpt6, causing syndromic NDD 38 unrelated individuals. Overexpression altered human hippocampal neuron morphology, while knockdown led...
Abstract Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants the two genes that encode histone H3.3 ( H3-3A / H3F3A and H3-3B H3F3B ) [1–4]. This characterized developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, abnormal neuroimaging [1, 5]. BLBS was initially categorized as a progressive neurodegenerative de novo heterozygous either or Here, we analyze data of 58 previously published...
Journal Article Highly conserved 3′ UTR and expression pattern of FXR1 points to a divergent gene regulation FMR1 Get access Johannes F. Coy, Coy Deutsches KrebsforschungszentrumIm Neuenheimer Feld 280, D-69120 Heidelberg Search for other works by this author on: Oxford Academic PubMed Google Scholar Zdenek Sedlacek, Sedlacek Dietmar Bächner, Bächner 1Abteilung Medizinische Genetik, Universität Ulm069 Ulm, Germany Horst Hameister, Hameister Stefan Joos, Joos Peter Lichter, Lichter Hajo...
Abstract BACKGROUND. A decrease in the age at cancer onset and increase incidence successive generations Li‐Fraumeni syndrome (LFS) families with germline TP53 mutations have been previously described. In current study a possible relation was analyzed between telomere length mutation carriers. METHODS. Telomere measured using real‐time quantitative polymerase chain reaction (PCR) 20 carriers of 83 unrelated healthy individuals. According to blood sampling, patients controls were divided into...
The Czech Republic has one of the highest incidences colorectal cancer (CRC) in Europe. To evaluate whether sporadic CRCs patients have specific mutational profiles we analysed somatic genetic changes known CRC genes (APC, KRAS, TP53, CTNNB1, MUTYH and BRAF, loss heterozygosity (LOH) at APC locus, microsatellite instability (MSI), methylation MLH1 promoter) 103 tumours from 102 individuals. most frequently mutated gene was (68.9% tumours), followed by KRAS (31.1%), TP53 (27.2%), BRAF (8.7%)...