Eva Maria Christina Schwaibold
A5077135904- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Neurogenetic and Muscular Disorders Research
- Epigenetics and DNA Methylation
- Cell Adhesion Molecules Research
- Chromatin Remodeling and Cancer
- Ocular Disorders and Treatments
- RNA Research and Splicing
- Cancer-related gene regulation
- Fetal and Pediatric Neurological Disorders
- Neurological disorders and treatments
- melanin and skin pigmentation
- Genetic Syndromes and Imprinting
- RNA and protein synthesis mechanisms
- Neonatal and fetal brain pathology
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Skin Diseases and Diabetes
- Autism Spectrum Disorder Research
- Inflammatory Myopathies and Dermatomyositis
- Dermatological and Skeletal Disorders
- Prenatal Screening and Diagnostics
- Cancer and Skin Lesions
- Genomics and Phylogenetic Studies
Heidelberg University
2008-2024
University Hospital Heidelberg
2019-2024
Institute of Human Genetics
2024
University of Tübingen
2021-2023
Lurie Children's Hospital
2023
Maastricht University
2022
University of California, Los Angeles
2021
Goethe University Frankfurt
2021
Klinikum rechts der Isar
2021
University of Cologne
2021
Abstract Individuals with ultrarare disorders pose a structural challenge for healthcare systems since expert clinical knowledge is required to establish diagnoses. In TRANSLATE NAMSE, 3-year prospective study, we evaluated novel diagnostic concept based on multidisciplinary expertise in Germany. Here present the systematic investigation of phenotypic and molecular genetic data 1,577 patients who had undergone exome sequencing were partially analyzed next-generation phenotyping approaches....
About 3% of newborns show malformations, with about 20% the affected having genetic causes. Clarification diseases in postnatal diagnostics was significantly improved high-throughput sequencing, particular through whole exome sequencing covering all protein-coding regions. Here, we aim to extend use this technology prenatal diagnostics.Between 07/2018 and 10/2020, 500 pregnancies fetal ultrasound abnormalities were analyzed after counseling as part using WES fetus parents.Molecular findings...
Fetal akinesia (FA) results in variable clinical presentations and has been associated with more than 166 different disease loci. However, the underlying molecular cause remains unclear many individuals. We aimed to further define set of genes involved.We performed in-depth characterisation exome sequencing on a cohort 23 FA index cases sharing arthrogryposis as common feature.We identified likely pathogenic or variants 12 established explaining phenotype 13 report novel variants. In...
Dystonia is a prevalent, heterogeneous movement disorder characterized by involuntarily abnormal postures. Biomarkers of dystonia are notoriously lacking. Here, biomarker reported for histone lysine methyltransferase (KMT2B)-deficient dystonia, leading subtype among the individually rare monogenic dystonias. It was derived applying support vector machine to an episignature 113 DNA CpG sites, which, in blood cells, showed significant epigenome-wide association with KMT2B deficiency and at...
Terminal deletions of chromosome 3p26.3 confined to the <i>CHL1</i> gene have previously been described in children with intellectual disability and epilepsy. Here, we report for first time, a duplication including only an intellectually disabled girl The penetrance both duplications is reduced because all chromosomal imbalances were inherited from healthy parents. Further studies are needed specify pathogenic mechanism estimate recurrence risks genetic counseling. However, description...
Exome sequencing and Drosophila modeling revealed variants in SMARCA5 as a novel cause of neurodevelopmental disorder.
Abstract Most individuals with rare diseases initially consult their primary care physician. For a subset of diseases, efficient diagnostic pathways are available. However, ultra-rare often require both expert clinical knowledge and comprehensive genetic diagnostics, which poses structural challenges for public healthcare systems. To address these within Germany, novel structured concept, based on multidisciplinary expertise at established university hospital centers (CRDs), was evaluated in...
Summary Many neurodevelopmental defects are linked to perturbations in genes involved housekeeping functions, such as those encoding ribosome biogenesis factors. However, how reductions can result tissue and developmental specific remains a mystery. Here we describe new allelic variants the factor AIRIM primarily associated with disorders. Using human cerebral organoids combination proteomic analysis, single-cell transcriptome analysis across multiple stages, single organoid translatome...
Kleefstra syndrome is characterized by intellectual disability, muscular hypotonia in childhood and typical facial features. It results from either a microdeletion of or deleterious sequence variant the gene euchromatic histone-lysine N-methyltransferase 1 (EHMT1) on chromosome 9q34.We report 3-year-old girl with characteristic symptoms syndrome. Array comparative genomic hybridization analysis revealed 145 kilobases duplication spanning exons 2 to 10 EHMT1. Sequence it as an intragenic...
Our objective was to improve rare variant interpretation using statistical measures as well publicly accessible annotation of expression levels and tissue specificity different splice isoforms. We describe VPS16 variants observed in patients with dystonia without dystonia, elaborate on our affecting transcripts, provide detailed clinical description the movement disorder caused by variants.In-house exome genome data sets (n = 11,539) were screened for heterozygous missense putative...
Recently, others and we identified de novo FBXO11 (F-Box only protein 11) variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability the core feature behavioral anomalies, hypotonia various facial dysmorphism frequent aspects. includes intragenic deletions, likely gene disrupting missense...
Abstract Objective Epilepsy is common in patients with PIGN diseases due to biallelic variants; however, limited epilepsy phenotyping data have been reported. We describe the epileptology of encephalopathy. Methods recruited variants and obtained clinical regarding age at seizure onset/offset semiology, development, medical history, examination, electroencephalogram, neuroimaging, treatment. Seizure types were classified. Results Twenty six (13 female) from 26 families identified, mean 7...
Background . We report a case of multiple keratocysts first diagnosed in an 8-year-old boy. Case The incidental radiographic finding cystic lesion boy led to the surgical enucleation and further diagnosis keratocyst associated with tooth crown. In course dental maturation from deciduous permanent teeth, presented new lesions, always crowns teeth. Gorlin-Goltz (nevoid basal-cell carcinoma) syndrome was suspected, genetic analysis detected previously undescribed germline variant PTCH1 gene....
X-linked myotubular myopathy (XLMTM) is a rare hereditary disorder of the skeletal muscle. Symptoms include impaired respiration and muscular hypotonia, usually present at birth leading to death during infancy or early childhood.1 Pneumothorax, defined as trapping air in pleural cavity, can be caused by surgery occur spontaneously.2 Pneumothorax has been reported only small number cases with myopathies, but not spontaneously never XLMTM.
Reported cases of "pure" duplication the entire short arm chromosome 16 (16p) are rare, with only 7 patients described in literature. We report on a female infant de novo 16p localized to 6, detected by chromosomal analysis and characterized array CGH fluorescence situ hybridization. This baby girl presented clinical symptoms characteristic duplications 16: psychomotor retardation, constitutional growth delay specific dysmorphic features, including proximally placed hypoplastic thumbs. In...
Biallelic pathogenic variants in SZT2 result a neurodevelopmental disorder with shared features, including early-onset epilepsy, developmental delay, macrocephaly, and corpus callosum abnormalities. is as critical scaffolding protein the amino acid sensing arm of mTORC1 signalling pathway. Due to its large size (3432 acids), lack crystal structure, absence functional domains, it difficult determine pathogenicity missense in-frame deletions, but these are increasingly detected reported by...