Michael Zech
A5006018069- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Neurological disorders and treatments
- Genetic Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- Neurological diseases and metabolism
- Neurogenetic and Muscular Disorders Research
- Mitochondrial Function and Pathology
- Congenital heart defects research
- RNA regulation and disease
- Metabolism and Genetic Disorders
- Genomic variations and chromosomal abnormalities
- Hereditary Neurological Disorders
- Botulinum Toxin and Related Neurological Disorders
- RNA and protein synthesis mechanisms
- Cellular transport and secretion
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Ion channel regulation and function
- Lysosomal Storage Disorders Research
- ATP Synthase and ATPases Research
- Congenital Heart Disease Studies
- Biochemical and Molecular Research
Helmholtz Zentrum München
2016-2025
Technical University of Munich
2016-2025
Institute for Advanced Study
2023-2025
Klinikum rechts der Isar
2013-2024
John Wiley & Sons (United States)
2020-2024
Schön Klinik Vogtareuth
2023
Universität Innsbruck
1976-2023
Innsbruck Medical University
2023
Centre for Movement Disorders
2023
Institute of Human Genetics
2021
ABSTRACT Background Dystonia is clinically and genetically heterogeneous. Despite being a first‐line testing tool for heterogeneous inherited disorders, whole‐exome sequencing has not yet been evaluated in dystonia diagnostics. We set up pilot study to address the yield of early‐onset generalized dystonia, disease subtype enriched monogenic causation. Methods Clinical coupled with bioinformatics analysis detailed phenotyping mutation carriers was performed on 16 consecutive cases undefined...
Up to 40% of neurodevelopmental disorders (NDDs) such as intellectual disability, developmental delay, autism spectrum disorder, and motor abnormalities have a documented underlying monogenic defect, primarily due de novo variants. Still, the overall burden variants well novel disease genes in NDDs await discovery. We performed parent-offspring trio exome sequencing 231 individuals with NDDs. Phenotypes were compiled using human phenotype ontology terms. The diagnostic yield was 49.8% (n =...
Objectives The majority of people with suspected genetic dystonia remain undiagnosed after maximal investigation, implying that a number causative genes have not yet been recognized. We aimed to investigate this paucity diagnoses. Methods undertook weighted burden analysis whole‐exome sequencing (WES) data from 138 individuals unresolved generalized etiology, followed by additional case‐finding international databases, first for the gene implicated ( VPS16 ), and then other functionally...
Objective Genetic dystonia is a complex movement disorder with diverse clinical manifestations resulting from pathogenic mutations in associated genes. A recent paradigm shift emphasizes the functional convergence among genes, hinting at shared pathomechanism. However, neural dynamics supporting this remain largely unexplored. Methods Herein, we analyzed microelectrode recordings acquired during pallidal deep brain stimulation surgery 31 patients AOPEP , GNAL KMT2B PANK2 PLA2G6 SGCE THAP1...
Niemann-Pick type C (NPC) disease is a rare autosomal-recessively inherited lysosomal storage disorder caused by mutations in NPC1 (95%) or NPC2. Given the highly variable phenotype, diagnosis challenging and particularly late-onset forms with predominantly neuropsychiatric presentations are likely underdiagnosed. Pathophysiologically, genetic alterations compromising endosomal/lysosomal system linked age-related neurodegenerative disorders. We sought to examine possible association of...
Abstract DNA methylation classifiers (“episignatures”) help to determine the pathogenicity of variants uncertain significance (VUS). However, their sensitivity is limited due training on unambiguous cases with strong-effect so that classification reduced effect size or in mosaic state may fail. Moreover, episignature evaluation mosaics as a function degree mosaicism has not been developed far. We improved episignatures respect three categories. Applying (i)...
ABSTRACT Background Rare autosomal‐dominant mutations in ANO3 and GNAL have been recently shown to represent novel genetic factors underlying primary torsion dystonia (PTD) with predominantly craniocervical involvement. Methods We used high‐resolution melting screen all exons of for rare sequence variants a population 342 German individuals mainly sporadic PTD 376 general controls. Results identified 2 missense (p.Ile833Val p.Gly973Arg) 1 variant (p.Val146Met) three different nonfamilial...
Recessive DYT16 dystonia associated with mutations in PRKRA has until now been reported only seven Brazilian patients. The aim of this study was to elucidate the genetic cause underlying disease a Polish family autosomal-recessive, early-onset generalized and slight parkinsonism, explore further role series European ancestry. We employed whole-exome sequencing two affected siblings filtered for rare homozygous compound heterozygous variants shared by both exomes. Validation identified as...
ABSTRACT Background : Recently a novel syndrome of childhood‐onset generalized dystonia originating from mutations in lysine‐specific methyltransferase 2B ( KMT2B ) has been reported. Methods We sequenced the exomes 4 dystonia‐affected probands recruited Prague movement disorders center (Czech Republic). Bioinformatics analyses were conducted to select candidate causal variants described dystonia‐mutated genes. After cosegregation testing, checklists American College Medical Genetics and...
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...
Abstract ATP5F1B is a subunit of the mitochondrial ATP synthase or complex V respiratory chain. Pathogenic variants in nuclear genes encoding assembly factors structural subunits are associated with deficiency, typically characterized by autosomal recessive inheritance and multisystem phenotypes. Movement disorders have been described subset cases carrying dominant ATP5F1A ATP5MC3. Here, we report identification two different missense (c.1000A>C; p.Thr334Pro c.1445T>C;...
Objective De novo variants in cullin‐3 ubiquitin ligase ( CUL3 ) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series reported so far. Here, we aimed to collect sporadic cases carrying rare , describe the genotype–phenotype correlation, and investigate underlying pathogenic mechanism. Methods Genetic data detailed clinical records were collected via multicenter collaboration. Dysmorphic facial features analyzed using GestaltMatcher. Variant effects...
Mutations and multiplications in the SNCA gene , encoding alpha-synuclein (aSyn), are associated with familial forms of Parkinson's disease (PD). We report identification a novel missense mutation (NM_000345.4, cDNA 174G>C; protein K58N) PD patient using whole exome sequencing, describe comprehensive molecular cellular analysss effects this mutation. The exhibited typical sporadic early onset benign course. Biophysical studies revealed that K58N substitution causes local structural effects,...