Mona Grimmel
A5043402771- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Neurogenetic and Muscular Disorders Research
- Glycogen Storage Diseases and Myoclonus
- RNA Research and Splicing
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- Metabolism and Genetic Disorders
- RNA modifications and cancer
- Genetics, Aging, and Longevity in Model Organisms
- Cellular transport and secretion
- Genomic variations and chromosomal abnormalities
- Neurological diseases and metabolism
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
- Neurological disorders and treatments
- Fetal and Pediatric Neurological Disorders
- Peptidase Inhibition and Analysis
- Pediatric Hepatobiliary Diseases and Treatments
- Health, Environment, Cognitive Aging
- Autoimmune Neurological Disorders and Treatments
- Coenzyme Q10 studies and effects
- Ocular Disorders and Treatments
- Endoplasmic Reticulum Stress and Disease
University of Tübingen
2015-2024
University of Wisconsin–Madison
2023
Lurie Children's Hospital
2023
University of Southern Denmark
2022
Universitätsklinikum Tübingen
2018
A recurrent de novo missense variant in KCNC1, encoding a voltage-gated potassium channel expressed inhibitory neurons, causes progressive myoclonus epilepsy and ataxia, nonsense is associated with intellectual disability. We identified three new variants KCNC1 five unrelated individuals causing different phenotypes featuring either isolated nonprogressive (p.Cys208Tyr), disability (p.Thr399Met), or myoclonic, absence generalized tonic-clonic seizures, developmental delay (p.Ala421Val,...
Missense variants in RNA-binding proteins (RBPs) underlie a spectrum of disease phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy. Here, we present ten independent families with severe, progressive muscular dystrophy, reminiscent oculopharyngeal dystrophy (OPMD) but much earlier onset, caused by heterozygous frameshift the RBP hnRNPA2/B1. All disease-causing mutations abolish native stop codon extend reading frame, creating novel...
Aminoacyl-tRNA synthetases (ARSs) are ubiquitous, ancient enzymes that charge amino acids to cognate tRNA molecules, the essential first step of protein translation. Here, we describe 32 individuals from 21 families, presenting with microcephaly, neurodevelopmental delay, seizures, peripheral neuropathy, and ataxia, de novo heterozygous bi-allelic mutations in asparaginyl-tRNA synthetase (NARS1). We demonstrate a reduction NARS1 mRNA expression as well enzyme levels activity both individual...
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...
Abstract Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting reduced or complete loss-of-function (LOF) of encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype both males females. Through international clinical matchmaking interrogation public variant databases we assembled database 90 rare missense families: 41 unique 18 recurrent 49 families. For 43 families, including 22 33 females, collated detailed...
Neurodevelopmental disorders are major indications for genetic referral and have been linked to more than 1500 loci including genes encoding transcriptional regulators. The dysfunction of transcription factors often results in characteristic syndromic presentations; however, at least half these patients lack a diagnosis. implementation machine learning approaches has the potential aid identification new disease delineate associated phenotypes. Next generation sequencing was performed seven...
Human coenzyme Q4 (COQ4) is essential for Q10 (CoQ10) biosynthesis. Pathogenic variants in COQ4 cause childhood-onset neurodegeneration. We aimed to delineate the clinical spectrum and cellular consequences of deficiency.Clinical course neuroradiological findings a large cohort paediatric patients with deficiency were analysed. Functional studies patient-derived cell lines performed.We characterised 44 individuals from 36 families (16 newly described). A total 23 different identified,...
Abstract The von Willebrand Factor A domain containing 1 protein, encoded by VWA1, is an extracellular matrix protein expressed in muscle and peripheral nerve. It interacts with collagen VI perlecan, two proteins that are affected hereditary neuromuscular disorders. Lack of VWA1 known to compromise nerves a Vwa1 knock-out mouse model. Exome sequencing led us identify bi-allelic loss function variants as the molecular cause underlying so far genetically undefined disorder. We detected six...
We present a female patient in her early twenties with global development delay, progressive ataxia, epilepsy, and myoclonus caused by stop mutation the SEMA6B gene. Truncating DNA variants located last exon of have recently been identified as cause autosomal dominant epilepsy. In many cases, context myoclonic epilepsy is refractory to medical treatment. case, treatment zonisamide clinical improvement, particularly positive negative truncal myoclonus, considerably improving patient's gait...
To examine the diagnostic yield of trio exome sequencing in fetuses with multiple structural defects no pathogenic findings cytogenetic and microarray analyses.We recruited 51 two or more defects, non-immune fetal hydrops akinesia deformation syndrome|or sequence (FADS). Trio was performed on DNA from chorionic villi samples parental blood. Detection genomic variation prioritization clinically relevant variants according to in-house standard operating procedures.Median maternal gestational...
Intellectual disability (ID) occurs in approximately 1% of the population. Over last years, broad sequencing approaches such as whole exome (WES) substantially contributed to definition molecular defects underlying nonsyndromic ID. Pathogenic variants HIVEP2, which encodes human immunodeficiency virus type I enhancer binding protein 2, have recently been reported a cause ID, developmental delay, behavioral disorders, and dysmorphic features. HIVEP2 serves transcriptional factor regulating...
Mitchell syndrome is a very rare genetic disorder due to specific de novo gain-of-function variant in acyl-CoA oxidase 1 (
During macroautophagy, the human WIPI (WD-repeat protein interacting with phosphoinositides) proteins (WIPI1–4) function as phosphatidylinositol 3-phosphate effectors at nascent autophagosome. Likewise, two homologues in Caenorhabditis elegans, ATG-18 and EPG-6, play important roles autophagy, whereby is considered to act upstream of EPG-6 onset autophagy. Due its essential role was found be also for lifespan extension elegans; however, this has not yet been addressed regard EPG-6. Here, we...
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...
Recently, Muñoz-Oreja et al. 1 reported that elevated cholesterol functions as a compensatory mechanism to increase tolerance pathological heterozygous dominant-acting ATAD3A variants, eventually leading membrane-embedded aggregation in the form of membrane whorls.This excess is cellular and abnormality ATAD3-associated disorder can cascade lysosomal insufficiency.Here we present similar accumulation free whorls two unrelated patients' cells carrying biallelic variants.Our results suggest...
Introduction: Glycogen storage disease type VI (GSD VI) is a disorder of glycogen metabolism due to mutations in the PYGL gene. Patients with GSD usually present hepatomegaly, recurrent hypoglycemia, and short stature. Results: We report on two non-related Turkish patients novel homozygous splice site variant, c.345G>A, which was shown lead exon 2 skipping PYGL-mRNA by exome transcriptome analysis. According an silico analysis, deletion Arg82_Gln115del predicted impair protein stability...