Saskia Biskup
A5052522766- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Cancer Genomics and Diagnostics
- Parkinson's Disease Mechanisms and Treatments
- Genomic variations and chromosomal abnormalities
- Neurological diseases and metabolism
- Alzheimer's disease research and treatments
- Genetic Neurodegenerative Diseases
- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Mitochondrial Function and Pathology
- Cancer Immunotherapy and Biomarkers
- Metabolism and Genetic Disorders
- Retinal Development and Disorders
- RNA regulation and disease
- Genetic factors in colorectal cancer
- Retinal Diseases and Treatments
- Immunotherapy and Immune Responses
- Epilepsy research and treatment
- Neurological disorders and treatments
- RNA modifications and cancer
- Connective tissue disorders research
- Hereditary Neurological Disorders
- Cellular transport and secretion
- Ion channel regulation and function
CeGaT (Germany)
2016-2025
Praxis für Humangenetik Tübingen
2016-2025
Bernstein Center for Computational Neuroscience Tübingen
2013-2025
Genomics (United Kingdom)
2013-2024
Hertie Institute for Clinical Brain Research
2011-2023
University of Tübingen
2009-2023
German Center for Neurodegenerative Diseases
2010-2019
Marche Polytechnic University
2018
University College London
2018
Katharinenhospital
2018
Mutations in the leucine-rich repeat kinase 2 gene ( LRRK2 ) cause late-onset Parkinson's disease (PD) with a clinical appearance indistinguishable from idiopathic PD. Initial studies suggest that mutations are most common yet identified determinant of PD susceptibility, transmitted an autosomal-dominant mode inheritance. Herein, we characterize and transcript human brain subclone predominant ORF. Exogenously expressed protein migrates at ≈280 kDa is present largely cytoplasm but also...
Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) cause late-onset Parkinson's disease indistinguishable from idiopathic disease. The mechanisms whereby missense alterations LRRK2 initiate neurodegeneration remain unknown. Here, we demonstrate that seven of 10 suspected familial-linked mutations result increased activity. Functional and disease-associated conserved residues reveal critical link between intrinsic guanosine triphosphatase (GTPase) activity downstream requires GTPase...
The PARK8 gene responsible for late-onset autosomal dominant Parkinson's disease encodes a large novel protein of unknown biological function termed leucine-rich repeat kinase 2 (LRRK2). studies herein explore the localization LRRK2 in mammalian brain.Polyclonal antibodies generated against amino or carboxy termini were used to examine biochemical, subcellular, and immunohistochemical distribution LRRK2.LRRK2 is detected rat brain as an approximate 280kDa by Western blot analysis....
There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into best practices in the areas of sequence data generation, analysis, interpretation reporting. The CLARITY Challenge was designed spur convergence diagnosing genetic disease starting from case history data. DNA samples were obtained three families with heritable disorders genomic donated by platform vendors....
Summary Purpose: Epilepsies have a highly heterogeneous background with strong genetic contribution. The variety of unspecific and overlapping syndromic nonsyndromic phenotypes often hampers clear clinical diagnosis prevents straightforward testing. Knowing the basis patient’s epilepsy can be valuable not only for but also guiding treatment estimating recurrence risks. Methods: To overcome these diagnostic restrictions, we composed panel genes Next Generation Sequencing containing most...
<h3>Background</h3> We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects <i>GRIN2B</i> encephalopathy explored potential prospects personalised medicine. <h3>Methods</h3> Data 48 individuals with de novo variants were collected from several diagnostic research cohorts, as well 43 patients the literature. Functional consequences response to memantine treatment investigated in vitro eventually translated into patient care. <h3>Results</h3> Overall, 86...
Alterations of the N-methyl-d-aspartate receptor (NMDAR) subunit GluN2A, encoded by GRIN2A, have been associated with a spectrum neurodevelopmental disorders prominent speech-related features, and epilepsy. We performed comprehensive assessment phenotypes standardized questionnaire in 92 previously unreported individuals GRIN2A-related disorders. Applying criteria American College Medical Genetics Genomics to all published variants yielded 156 additional cases pathogenic or likely resulting...
To determine the phenotypic spectrum caused by mutations in GRIN1 encoding NMDA receptor subunit GluN1 and to investigate their underlying functional pathophysiology.We collected molecular clinical data from several diagnostic research cohorts. Functional consequences of were investigated Xenopus laevis oocytes.We identified heterozygous de novo 14 individuals reviewed phenotypes all 9 previously reported patients. These 23 presented with a distinct phenotype profound developmental delay,...
<h3>Objective</h3> We aimed to delineate the neurodevelopmental spectrum associated with <i>SYNGAP1</i> mutations and investigate genotype–phenotype correlations. <h3>Methods</h3> sequenced exome or screened exons of in a total 251 patients disorders. Molecular clinical data from other centres were also collected, focusing on developmental aspects epilepsy phenotype. A review published literature was performed. <h3>Results</h3> describe 17 unrelated affected individuals carrying 13 different...
<h3>Background</h3> Metastasized or unresectable melanoma has been the first malignant tumor to be successfully treated with checkpoint inhibitors. Nevertheless, about 40–50% of patients do not respond these treatments and severe side effects are observed in up 60%. Therefore, there is a high need identify reliable biomarkers predicting response. Tumor Mutation Burden (TMB) debated predictor for response inhibitors early measurement ctDNA can help detect treatment failure immunotherapy...
Diminished hepatocyte regeneration is a key feature of acute and chronic liver diseases after extended resections, resulting in the inability to maintain or restore sufficient functional mass. Therapies are lacking, making transplantation only curative option for end-stage disease. Here, we report on structure-based development characterization (nuclear magnetic resonance [NMR] spectroscopy) first-in-class small molecule inhibitors dual-specificity kinase MKK4 (MKK4i). MKK4i increased upon...
Mutations in SACS, leading to autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), have been identified as a frequent cause recessive early-onset around the world. Here we aimed enlarge spectrum SACS mutations outside Quebec, establish pathogenicity novel variants, and expand clinical imaging phenotype.Sequencing 22 patients with unexplained ataxia, assessment variants 3.500 European control chromosomes extensive phenotypic investigations all carriers.We 11 index harbouring 17...
Mutations within the leucine-rich repeat kinase 2 (LRRK2) gene account for a significant proportion of autosomal-dominant and some late-onset sporadic Parkinson's disease. Elucidation LRRK2 protein function in health disease provides an opportunity deciphering molecular pathways important neurodegeneration. In mammals, LRRK1 comprise unique family encoding GTPase domain that controls intrinsic activity. The expression profiles murine LRRK proteins have not been fully described insufficiently...
Mutations in LRRK2 cause autosomal dominant Parkinson's disease (PD). encodes a multi-domain protein containing GTPase and kinase domains, putative protein-protein interaction domains. Familial PD mutations alter the activity of vitro. is suggested to regulate number cellular pathways although underlying mechanisms are poorly understood. To explore such mechanisms, it has proved informative identify LRRK2-interacting proteins, some which serve as substrates. Here, we common interactions with...
<h3>Objective</h3> To characterize the neurologic phenotypes associated with <i>COL4A1/2</i> mutations and to seek genotype–phenotype correlation. <h3>Methods</h3> We analyzed clinical, EEG, neuroimaging data of 44 new 55 previously reported patients <i>COL4A1/COL4A2</i> mutations. <h3>Results</h3> Childhood-onset focal seizures, frequently complicated by status epilepticus resistance antiepileptic drugs, was most common phenotype. EEG typically showed epileptiform discharges in context...
We aimed to unravel the molecular genetic basis of inherited retinal degeneration (IRD) in a comprehensive cohort patients diagnosed largest center for IRD Germany. A 2,158 affected from 1,785 families with was analyzed by targeted next-generation sequencing (NGS). Patients single-gene disorders (i.e., choroideremia and retinoschisis) were Sanger multiplex ligation-dependent probe amplification. Our study accounts ∼7% estimated 30,000 Germany, thereby providing representative data both...
PurposePhenotype information is crucial for the interpretation of genomic variants. So far it has only been accessible bioinformatics workflows after encoding into clinical terms by expert dysmorphologists.MethodsHere, we introduce an approach driven artificial intelligence that uses portrait photographs exome data. We measured value added computer-assisted image analysis to diagnostic yield on a cohort consisting 679 individuals with 105 different monogenic disorders. For each case in...
Abstract Variants in RAC3, encoding a small GTPase RAC3 which is critical for the regulation of actin cytoskeleton and intracellular signal transduction, are associated with rare neurodevelopmental disorder structural brain anomalies facial dysmorphism. We investigated cohort 10 unrelated participants presenting global psychomotor delay, hypotonia, behavioural disturbances, stereotyped movements, dysmorphic features, seizures musculoskeletal abnormalities. MRI revealed complex pattern...
Mutations in the leucine-rich repeat kinase 2 ( LRRK2 ) gene are most common known cause of Parkinson's disease (PD). Whether loss function accounts for neurodegeneration dopamine neurons PD is not known, nor it whether activity modulates susceptibility (DA) to selective dopaminergic toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To better understand role DA neuronal survival and its MPTP, we generated knock-out (KO) mice lacking domain LRRK2. Here, show that KO viable have no...