A5021602752- Genomic variations and chromosomal abnormalities
- Prenatal Screening and Diagnostics
- Genomics and Rare Diseases
- Ear Surgery and Otitis Media
- Hearing, Cochlea, Tinnitus, Genetics
- BRCA gene mutations in cancer
- Genetics and Neurodevelopmental Disorders
- Connective tissue disorders research
- Vestibular and auditory disorders
- Biomedical Text Mining and Ontologies
- Congenital heart defects research
- Biochemical and Molecular Research
- Genetic Syndromes and Imprinting
- Autism Spectrum Disorder Research
- Craniofacial Disorders and Treatments
- Nutrition, Genetics, and Disease
- Congenital limb and hand anomalies
- Hereditary Neurological Disorders
- Nuclear Structure and Function
- Tuberous Sclerosis Complex Research
- Genetic factors in colorectal cancer
- Iron Metabolism and Disorders
- Amino Acid Enzymes and Metabolism
- Rings, Modules, and Algebras
- Congenital Ear and Nasal Anomalies
Charles University
2010-2023
General University Hospital in Prague
2022
University Hospital in Motol
2021
Background Axenfeld-Rieger syndrome (ARS) is characterised by typical anterior segment anomalies, with or without systemic features. The discovery of causative genes identified ARS subtypes distinct phenotypes, but our understanding incomplete, complicated the rarity condition. Methods Genetic and phenotypic characterisation largest reported cohort through comprehensive genetic clinical data analyses. Results 128 individuals variants in PITX2 FOXC1 , including 81 new cases, were...
Abstract Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms childhood-onset and hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis clinical, imaging molecular data 156 patients from 101 families. Enrolled were diverse ethnic backgrounds covered wide age range (1.0–49.3 years). While mean at symptom...
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....
Summary Mutations in SLC26A4 cause Pendred syndrome (PS) – hearing loss with goitre or DFNB4 non‐syndromic (NSHL) inner ear abnormalities such as Enlarged Vestibular Aqueduct (EVA) Mondini Dysplasia (MD). We tested 303 unrelated Czech patients early (298 NSHL and 5 PS), all GJB2 ‐negative, for mutations evaluated their clinical radiological phenotype. Among 115 available HRCT/MRI scans we detected three MD (2.6%), Mondini‐like affections 16 EVA (13 bilateral 19.2% 15.6% respectively) 61...
Kabuki syndrome (KS) is a dominantly inherited disorder mainly due to de novo pathogenic variation in KMT2D or KDM6A genes. Initially, representative cohort of 14 Czech cases with clinical features suggestive KS was analyzed by experienced geneticists collaboration other specialties, and observed disease were evaluated according the 'MLL2-Kabuki score' defined Makrythanasis et al. Subsequently, aforementioned genes Sanger sequenced copy number analysis performed MLPA, followed genome-wide...
Abstract We report the clinical findings of 26 individuals from 16 unrelated families carrying variants in COL2A1 or COL11A1 genes. Using Sanger and next‐generation sequencing, 11 different (seven novel), were identified 13 (19 affected individuals), all diagnosed with Stickler syndrome (STL) type 1. In nine families, disease‐causing variant arose de novo. Phenotypically, we observed myopia (95%) retinal detachment (47%), joint hyperflexibility (92%), midface retrusion (84%), cleft palate...
Folate deficiency in the critical developmental period has been repeatedly associated with an increased risk of Autism spectrum disorders (ASD), but key pathophysiological mechanism not yet identified. In this work, we focused on identifying genes whose defect similar consequences to folate depletion metabolic network. Within Flux Balance Analysis (FBA) framework, developed a method blocked metabolites that allowed us define various gene defects and depletion. We identified six (GART, PFAS,...
Recently, cerebral folate deficiency (CFD) was suggested to be involved in the pathogenesis of autism spectrum disorders (ASD). However, exact role metabolism ASD, identification underlying pathogenic mechanisms and impaired metabolic pathways remain unexplained. The aim our study develop test a novel, unbiased, bioinformatics approach order identify links between ASD disturbed by focusing on abnormal metabolism, which could foster patient stratification novel therapeutic interventions. An...
We identified a de novo deletion of 14q11.2 in Czech patient with developmental delay, mild autistic features, macrosomy, macrocephaly, orthognathic deformities, and dysmorphic facial features. The clinical follow-up the lasting 14 years documented changes dysmorphism from infancy to adolescence. affects approximately 200 kb DNA five protein-coding genes two snoRNA genes. Two genes, SUPT16H CHD8, have been proposed as candidate for new microdeletion syndrome. Our further supports existence...
Abstract The communication of genomic results to patients and families with rare diseases raise distinctive challenges. However, there is little evidence about optimal methods communicate this group service users. To address gap, we worked disease health professionals from two genetic/genomic services, one in the United Kingdom Czech Republic, co-design that best meet their needs. Using participatory methodology Experience-Based Co-Design (EBCD), conducted observations clinical appointments...
Abstract Background Hearing loss is a common inborn neurosensory condition. very heterogeneous, and while screening programs exist for children, adolescents adults with late-onset hearing often do not get referrals to geneticists. Objective To diagnose the cause of impairment in two related patients—father son—on molecular level. Both underwent audiological examinations, both had moderate loss. Case presentation. We used massive parallel sequencing, Sanger MLPA, standard methods. identified...
With only 11 patients reported, 5p tetrasomy belongs to rare postnatal findings. Most cases are due small supernumerary marker chromosomes (sSMCs) or isochromosomes. The share common but unspecific symptoms such as developmental delay, seizures, ventriculomegaly, hypotonia, and fifth finger clinodactyly. Simple interstitial duplications leading trisomies of parts much more frequent better described. Duplications encompassing 5p13.2 cause a defined syndrome with macrocephaly, distinct facial...
The prenatal finding of a small supernumerary marker chromosome (sSMC) is challenge for genetic counseling. Our analytic algorithm based on sSMC frequencies and multicolor FISH to accelerate the procedure. chromosomal origin, size, degree mosaicism then determine prognosis. We illustrate effectiveness 4 prenatally identified de novo mosaic sSMCs derived from chromosomes 13/21, X, 3, 17. Three carriers had good prognosis apparently healthy children were born, showing no abnormality till last...
Myotonic dystrophy type 1 (DM1) belongs to the broad spectrum of genetic disorders associated with autism (ASD). ASD were reported predominantly in congenital and early childhood forms DM1. We describe dizygotic twin boys who referred for routine laboratory testing whom karyotyping, FMR1 gene testing, single nucleotide polymorphism array analysis yielded negative results. The father was later diagnosed suspected DM1, revealed characteristic DMPK expansions his genome as well genomes both...
Aims: Patients with the Pendred syndrome suffer very often from a hearing loss.They may be good candidates for cochlear implantation, but unfortunately, due to fluctuating character of loss, they escape such indication.In study, we compared speech production and acquisition in 2 groups implanted patients: those syndrome, standard non-syndromic patients.Methods: Ten patients were analyzed perception production.The control group consisted 41 patients.All implantees scored according perception,...