A5073308226- Metabolism and Genetic Disorders
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- RNA modifications and cancer
- Amino Acid Enzymes and Metabolism
- Genetic Neurodegenerative Diseases
- Child and Adolescent Health
- Epigenetics and DNA Methylation
- Neurogenetic and Muscular Disorders Research
- RNA regulation and disease
- Mitochondrial Function and Pathology
- Metabolomics and Mass Spectrometry Studies
- Health and Medical Studies
- Biochemical and Molecular Research
- Medical and Health Sciences Research
- Congenital Anomalies and Fetal Surgery
- Adolescent and Pediatric Healthcare
- CRISPR and Genetic Engineering
- Medical Imaging and Pathology Studies
- Genomic variations and chromosomal abnormalities
- Fetal and Pediatric Neurological Disorders
- Connective tissue disorders research
- Climate Change and Health Impacts
- Cardiac electrophysiology and arrhythmias
- Genetic Associations and Epidemiology
University Hospital Heidelberg
2018-2025
Heidelberg University
2018-2025
Institute of Human Genetics
2023
Universitätsmedizin Göttingen
2023
German Center for Pediatric and Adolescent Rheumatology
2022
Zentrum für Kinderheilkunde
2021
University of Tübingen
2014-2015
Hertie Institute for Clinical Brain Research
2014
Abstract Hao‐Fountain syndrome (HAFOUS, OMIM: #616863) is a neurodevelopmental disorder caused by pathogenic variants in the gene USP7 coding for USP7, protein involved several crucial cellular homeostatic mechanisms and recently described MUST complex. The phenotype of HAFOUS insufficiently understood, yet there great need to better understand spectrum disease, genotype–phenotype correlations, disease trajectories. We now present larger cohort 32 additional individuals provide further...
Abstract Genomic newborn screening (gNBS) is on the horizon given decreasing costs of sequencing and advanced understanding impact genetic variants health diseases. Key to ongoing gNBS pilot studies selection target diseases associated genes be included. In this study, we present a comprehensive analysis seven published gene–disease lists from studies, evaluating count, composition, group proportions, ClinGen curations individual disorders. Despite shared criteria, observe substantial...
Abstract The objective of the study is to evaluate evolving phenotype and genetic spectrum patients with succinic semialdehyde dehydrogenase deficiency (SSADHD) in long‐term follow‐up. Longitudinal clinical biochemical data 22 pediatric 9 adult individuals SSADHD from patient registry International Working Group on Neurotransmitter related Disorders (iNTD) were studied silico analyses, pathogenicity scores molecular modeling ALDH5A1 variants. Leading initial symptoms, onset infancy,...
ABSTRACT (Likely) pathogenic variants in NR2F1 are associated with Bosch‐Boonstra‐Schaaf optic atrophy syndrome (BBSOAS, OMIM #615722), a rare neurodevelopmental disorder. Patients present variety of symptoms, including intellectual disability, developmental delay, visual impairment, muscular hypotonia, seizures, and/or autistic features. Since it was first described 2014, the phenotype has steadily expanded. However, there is limited information regarding natural course Here, we data on...
Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel Kv1.2, have been identified as cause an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, movement disorders resulting from cerebellar dysfunction. In addition, with a milder course epilepsy, complicated hereditary spastic paraplegia, episodic ataxia reported. By analyzing phenotypic, functional, genetic data...
Aromatic l-amino-acid decarboxylase (AADC) deficiency is an inherited disorder of biogenic amine metabolism with a broad neurological phenotype. The clinical symptoms overlap other diseases resulting in often delayed diagnosis. Innovative disease-changing treatment options, particularly gene therapy, have emphasised the need for early We describe first method 3-O-methyldopa (3-OMD) analysis dried blood spots (DBS) suitable high throughput newborn screening (NBS). established novel tandem...
Abstract Background Pulmonary alveolar proteinosis (PAP) is a heterogeneous condition with more than 100 different underlying disorders that need to be differentiated target therapeutic options, which are generally limited. Methods The clinical course of two brothers pathogenic variants in the methionyl‐tRNA synthetase ( MARS)1 gene was compared previously published patients. Functional studies patient‐derived fibroblasts were performed and options evaluated. Results younger brother...
Abstract Mevalonic aciduria (MVA) and hyperimmunoglobulinemia D syndrome (MKD/HIDS) are disorders of cholesterol biosynthesis caused by variants in the MVK gene characterized increased urinary excretion mevalonic acid. So far, 30 MVA patients have been reported, suffering from recurrent febrile crises neurologic impairment. Here, we present an in‐depth analysis phenotypic spectrum provide in‐silico pathogenicity model missense variants. The 11 (age range 0‐51 years) registered Unified...
Abstract The autosomal recessive defect of aromatic L‐amino acid decarboxylase (AADC) leads to a severe neurological disorder with manifestation in infancy due pronounced, combined deficiency dopamine, serotonin and catecholamines. success conventional drug treatment is very limited, especially patients phenotype. development an intracerebral AAV2‐based gene delivery targeting the putamen or substantia nigra started more than 10 years ago. Recently, putaminally‐delivered construct,...
Abstract TUBA1A tubulinopathy is a rare neurodevelopmental disorder associated with brain malformations as well early-onset and intractable epilepsy. As pathomechanisms genotype-phenotype correlations are not completely understood, we aimed to provide further insights into the phenotypic genetic spectrum. We here present multicenter case series of ten unrelated individuals from four European countries using systematic MRI re-evaluation, protein structure analysis, prediction score modeling....
The widespread use of high-throughput sequencing techniques is leading to a rapidly increasing number disease-associated variants unknown significance and candidate genes. Integration knowledge concerning their genetic, protein as well functional conservational aspects necessary for an exhaustive assessment relevance prioritization further clinical studies investigating role in human disease. To collect the information, multitude different databases has be accessed data extraction from...
SYNCRIP encodes for the Synaptotagmin-binding cytoplasmic RNA-interacting protein, involved in RNA-binding and regulation of multiple cellular pathways. It has been proposed as a candidate gene neurodevelopmental disorders (NDDs) with autism spectrum disorder (ASD), intellectual disability (ID), epilepsy. We ascertained genetic, clinical, neuroradiological data three additional individuals novel de novo variants. All had ID. Autistic features were observed two. One individual showed...
This study aimed to define the genotypic and phenotypic spectrum of reversible acute liver failure (ALF) infancy resulting from biallelic pathogenic TRMU variants determine role cysteine supplementation in its treatment.
The inhibitor of nuclear factor kappa B zeta (IκBζ) is an atypical member the IκB protein family. Its function in regulating activity transcription (NFκB) as well its involvement cancer-associated processes poorly understood. In glioma patients, enhanced expression IκBζ tumor specimen associated with poor prognosis. Here we report that upregulated a cell line resistant towards NFκB-dependent non-apoptotic death. Upon γ-irradiation cells, enhanced, and subsequently serves transcriptional...
The X-linked form of Opitz BBB/G syndrome (OS) is a monogenic disorder in which symptoms are established early during embryonic development. OS caused by pathogenic variants the gene MID1 . Disease-associated distributed across entire locus, except for N-terminal really interesting new (RING) domain that encompasses E3 ubiquitin ligase activity. By using genome-edited human induced pluripotent stem cell lines, we here show absence isoforms containing RING causes severe patterning defects...