A5010209112- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Reproductive Physiology in Livestock
- Metabolism and Genetic Disorders
- RNA regulation and disease
- RNA modifications and cancer
- Glioma Diagnosis and Treatment
- interferon and immune responses
- Ion channel regulation and function
- Genetic Associations and Epidemiology
- CRISPR and Genetic Engineering
- Fetal and Pediatric Neurological Disorders
- Cardiac electrophysiology and arrhythmias
- Testicular diseases and treatments
- Sentiment Analysis and Opinion Mining
- Autophagy in Disease and Therapy
- Urologic and reproductive health conditions
- Congenital heart defects research
- Glycogen Storage Diseases and Myoclonus
- Machine Learning in Healthcare
- Histiocytic Disorders and Treatments
- Lipid metabolism and disorders
- Inflammasome and immune disorders
- Neurological diseases and metabolism
- Genetic Neurodegenerative Diseases
Heidelberg University
2012-2025
University Hospital Heidelberg
2012-2025
FOM University of Applied Sciences for Economics and Management
2024
MSB Medical School Berlin
2015
Heidelberg University
2012
Abstract Background Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder affecting multiple organ systems, with a prevalence of 1:6,760–1:13,520 live births in Germany. On the molecular level, TSC caused by heterozygous loss-of-function variants either genes TSC1 or TSC2 , encoding Tuberin-Hamartin complex, which acts as critical upstream suppressor mammalian target rapamycin (mTOR), key signaling pathway controlling cellular growth and metabolism. Despite therapeutic...
AimsHCN4 channels are involved in generation, regulation, and stabilization of heart rhythm channel dysfunction is associated with inherited sinus bradycardia. We asked whether dysfunctional HCN4 also contribute to the generation cardiac tachyarrhythmias.
Abstract Glutaric aciduria type 1 (GA1) is a rare neurometabolic disease caused by pathogenic variants in the gene encoding enzyme glutaryl‐CoA dehydrogenase (GCDH). We performed an extensive literature search to collect data on GA1 patients, together with unpublished cases, provide up‐to‐date genetic landscape of GCDH and investigate potential genotype‐phenotype correlation, as this still poorly understood. From search, 421 different have been identified, including four novel variants;...
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...
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 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....
Newborn screening (NBS) allows early identification of individuals with rare disease, such as isovaleric aciduria (IVA). Reliable prediction disease severity positively screened IVA is needed to guide therapeutic decision, prevent life-threatening neonatal manifestation in classic and over-medicalization attenuated that may remain asymptomatic. We analyzed 84 (median age at last study visit 8.5 years) confirmed identified by NBS between 1998 2018 who participated the national, observational,...
Abstract Brain organoids represent a useful tool for modeling of neurodevelopmental disorders and can recapitulate brain volume alterations such as microcephaly. To monitor organoid growth, brightfield microscopy images are frequently used evaluated manually which is time-consuming prone to observer-bias. Recent software applications evaluation address this issue using classical or AI-based methods. These pipelines have distinct strengths weaknesses that not evident external observers. We...
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...
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...
Pathogenic variants in PRRT2, encoding for the proline-rich transmembrane protein 2, were identified as main cause of self-limiting sporadic and familial infantile epilepsy. Reported data on treatment response to antiseizure medications (ASMs) defined monogenic epilepsies are limited. The aim this study was evaluate ASMs children with PRRT2-associated epilepsy.A multicenter, retrospective, cross-sectional cohort conducted according Strengthening Reporting Observational Studies Epidemiology...
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.
PurposeTUBA1A and TUBB2B tubulinopathies are rare neurodevelopmental disorders characterized by cortical extracortical malformations heterogenic phenotypes. There is a need for quantitative clinical endpoints that will be beneficial future diagnostic therapeutic trials.MethodsQuantitative natural history modeling of individuals with TUBA1A from reports database entries DECIPHER ClinVar. Main outcome measures were age at disease onset, survival, delay. Phenotypical, neuroradiological,...
Pathogenic variants in
WDR45-related neurodevelopmental disorder (NDD) is a clinically-heterogenous congenital of macroautophagy/autophagy. The natural history this ultra-orphan disease remains incompletely understood, leading to delays in diagnosis and lack quantifiable outcome measures. In cross-sectional study, we model quantitative data for NDD using standardized analysis 160 published cases, representing the largest cohort date. primary study was survival. Age at onset, diagnostic delay geographic...
Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare, monogenic disorder affecting the degradation of main inhibitory neurotransmitter γ-amino butyric acid (GABA). Pathogenic variants in ALDH5A1 gene that cause an enzymatic dysfunction succinic (SSADH) lead to accumulation potentially toxic metabolites, including γ-hydroxybutyrate (GHB). Here, we present patient with severe phenotype SSADHD caused by novel genetic variant c.728T > C leads exchange leucine proline at residue...
Identifying key statements in large volumes of short, user-generated texts is essential for decision-makers to quickly grasp their content. To address this need, research introduces a novel abstractive point generation (KPG) approach applicable unlabeled text corpora, using an unsupervised approach, feature not yet seen existing KPG methods. The proposed method uniquely combines topic modeling data space segmentation with summarization techniques efficiently generate semantically...
Hintergrund Tuberöse Sklerose (TSC) ist eine autosomal dominante genetische Erkrankung, die mehrere Organsysteme betrifft, mit einer Prävalenz von 1:6.760 bis 1:13.520 Lebendgeburten in Deutschland. Auf molekularer Ebene wird TSC durch einen Funktionsverlust den Genen TSC1 oder TSC2 verursacht, für Tuberin-Hamartin-Komplex kodieren, der als kritischer Upstream-Suppressor des Mammalian Target of Rapamycin (mTOR) -Signalwegs fungiert. Dies führt zu gestörter Hirnreifung Beeinträchtigung...
Variants in different neuronal tubulin isotypes cause severe neurodevelopmental disorders with cerebral malformations accompanied by developmental delay, motor impairment, and epilepsy, known as tubulinopathies. Induced pluripotent stem cells were generated from peripheral blood mononuclear a female subject carrying the heterozygous de novo variant c.[521C > T] (p.[Ala174Val]) TUBA1A gene. PBMCs reprogrammed using CytoTune™-iPS 2.0 Sendai Reprogramming Kit (Invitrogen) showed normal...