A5056436471- Lysosomal Storage Disorders Research
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Cellular transport and secretion
- Carbohydrate Chemistry and Synthesis
- Trypanosoma species research and implications
- Neurogenetic and Muscular Disorders Research
- RNA regulation and disease
- Metabolism and Genetic Disorders
- RNA Research and Splicing
- Child Nutrition and Feeding Issues
- Chromatin Remodeling and Cancer
- Glycogen Storage Diseases and Myoclonus
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Congenital heart defects research
- Hedgehog Signaling Pathway Studies
- Neonatal Health and Biochemistry
- Genetic Syndromes and Imprinting
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Biochemical and Molecular Research
- Mitochondrial Function and Pathology
- Tracheal and airway disorders
- Genetic Neurodegenerative Diseases
University of Tübingen
2014-2025
Universitätsklinikum Tübingen
2012-2024
German Center for Neurodegenerative Diseases
2020-2023
Ludwig-Maximilians-Universität München
2020-2023
University of Duisburg-Essen
2023
Friedrich Baur Stiftung
2023
University of Rostock
2023
Hertie Institute for Clinical Brain Research
2013-2020
University Hospital of Bern
2020
University Hospital Schleswig-Holstein
2020
<h2>ABSTRACT</h2><h3>Purpose</h3> Pathogenic variants in ARID1B are one of the most frequent causes intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data representative for identified through unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic phenotypic differences between ARID1B-ID ARID1B-CSS. In...
Disruptions of the FOXP2 gene, encoding a forkhead transcription factor, are first known monogenic cause speech and language disorder. So far, mainly chromosomal rearrangements such as translocations or larger deletions affecting have been reported. Intragenic convincingly pathogenic point mutations in up to date only reported three families. We thus aimed at further characterisation mutational clinical spectrum.Chromosomal microarray testing, trio exome sequencing, multigene panel...
To compare disease progression between different onset forms of metachromatic leukodystrophy (MLD) and to investigate the influence type first symptoms on natural course dynamic progression.
X-linked Charcot-Marie-Tooth disease type 5 (CMTX5), Arts syndrome, and non-syndromic sensorineural deafness (DFN2) are allelic syndromes, caused by reduced activity of phosphoribosylpyrophosphate synthetase 1 (PRS-I) due to loss-of-function mutations in PRPS1. As only few families have been described, knowledge about the relation between these phenotypic spectrum patients female carriers, underlying PRS-I is limited. We investigated a family with novel PRPS1 mutation (c.830A > C,...
Homozygous mutation of TBC1 domain-containing kinase (TBCK) is the cause a very recently defined severe childhood disorder, which characterized by hypotonia, global developmental delay, intellectual disability, epilepsy, characteristic facies and premature death. The link between TBCK loss function symptoms in patients with deficiency disorder (TBCK-DD) remains elusive. Here we demonstrate for first time histopathological characteristics consisting 1) widespread massive accumulation...
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...
In 2016 and 2018, Chung, Jansen others described a new syndrome caused by haploinsufficiency of PHIP (pleckstrin homology domain interacting protein, OMIM *612,870) mainly characterized developmental delay (DD), learning difficulties/intellectual disability (ID), behavioral abnormalities, facial dysmorphism obesity (CHUJANS, #617991). So far, alterations appear to be rare cause DD/ID. “Omics” technologies such as exome sequencing or array analyses have led the identification distinct types ,...
Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficiency of arylsulfatase A (ARSA). Subsequent accumulation sulfatides leads to demyelination and neurodegeneration in the central peripheral nervous system. To date MLD classified based on age at onset, however, especially for late onset forms this classification provides only limited projection regarding clinical course. Moreover, evolving newborn screening approaches raise need predict...
Abstract This report details the case of an infant with confirmed propionic acidemia who presented progressive neurological deterioration and recurrent episodes metabolic decompensation elevated lactate levels, but without hyperammonemia. The child's clinical course neuroradiological findings increasingly deviated from known spectrum acidemia. A rapid trio exome sequencing identified SLC19A3 ‐related thiamine metabolism dysfunction syndrome 2 as a second genetic disease. pathomechanisms both...
Metachromatic Leukodystrophy (MLD) is a rare autosomal-recessive lysosomal storage disorder caused by mutations in the ARSA gene. While interventional trials often use untreated siblings as controls, genotype-phenotype correlation only partly understood, and variability of clinical course between unclear with some evidence for discrepant juvenile patients. The aim this study was to systematically investigate phenotypic variation MLD comparison larger cohort case reports published literature....
Niemann-Pick type C (NPC) disease is a rare, usually fatal neurodegenerative lysosomal storage disorder. It inherited in an autosomal-recessive fashion and caused by mutation of either NPC1 (95%) or NPC2 gene.1 Age at onset broadly variable, ranging from neonatal neurovisceral manifestations to primarily adulthood that may be recognized as late 70 years age.1 Due its diverse clinical manifestation, correct diagnosis challenging, frequencies might underestimated, delayed, particular patients...
<h3>Objective:</h3> Identifying an intriguing mechanism for unmasking recessive hereditary spastic paraplegias. <h3>Method:</h3> Herein, we describe 4 novel homozygous <i>FA2H</i> mutations in nonconsanguineous families detected by whole-exome sequencing or a targeted gene panel analysis providing high coverage of all known paraplegia genes. <h3>Results:</h3> Segregation revealed cases only one parent as heterozygous mutation carrier whereas the other did not carry mutations. A macro...
Krabbe disease or globoid cell leukodystrophy is a severe neurodegenerative disorder caused by defect in the GALC gene leading to deficiency of enzyme ß-galactocerebrosidase. The aim this work was describe natural course covering whole spectrum disease.Natural history data were collected with standardized questionnaire, supplemented medical record data. We defined different forms according Abdelhalim et al. (2014). Developmental and trajectories described based on acquisition loss milestones...
MAGEL2-associated Schaaf-Yang syndrome (SHFYNG, OMIM #615547, ORPHA: 398069), which was identified in 2013, is a rare disorder caused by truncating variants of the paternal copy MAGEL2, localized imprinted region on 15q11.2q13. The phenotype SHFYNG childhood partially overlaps with that well-established Prader-Willi (PWS, #176270). While larger numbers younger individuals have been recently published, adulthood not well established. We recruited 7 adult (aged 18 to 36) molecularly confirmed...
To characterize subclinical abnormalities in asymptomatic heterozygote NPC1 mutation carriers as markers of neurodegeneration.Motor function, cognition, mood, sleep, and smell function were assessed 20 first-degree heterozygous relatives patients with Niemann-Pick disease type C (NPC) (13 male, age 52.7 ± 9.9 years). Video-oculography abdominal ultrasound volumetry performed to assess oculomotor size liver spleen. NPC biomarkers blood analyzed. 18F-fluorodesoxyglucose PET was (n = 16) detect...
Abstract Identification of prognostic or predictive molecular markers in glioblastoma resection specimens may lead to strategies for therapy stratification and personalized treatment planning. Here, we analyzed primary stem cell (pGSC) cultures the mRNA abundances seven (MSI1, Notch1, nestin, Sox2, Oct4, FABP7 ALDH1A3), three radioresistance invasion (CXCR4, IK Ca BK ). From these abundances, an signature was deduced which describes mesenchymal‐to‐proneural expression profile individual GSC...
GM2 gangliosidoses, a group of autosomal-recessive neurodegenerative lysosomal storage disorders, result from β-hexosaminidase (HEX) deficiency with ganglioside as its main substrate. Historically, gangliosidoses have been classified into infantile, juvenile, and late-onset forms. With disease-modifying treatment trials now on the horizon, more fine-grained understanding disease course is needed.
Decades ago, a family with three children neurovisceral lysosomal storage disease was described. The patient siblings died at ages 7, 9, and 11 years, respectively, according to the current concept had late-infantile neurologic form of Niemann-Pick type C1 (NPC) disease, given by present molecular study that there were severe NPC1 gene variants: Blood samples preserved since time from one sibling his presently 55-year-old essentially healthy sister have now been studied, revealing variants...
Abstract Filamin-A-interacting protein 1 (FILIP1) is a structural that involved in neuronal and muscle function integrity interacts with FLNa FLNc. Pathogenic variants filamin-encoding genes have been linked to neurological disorders (FLNA) diseases characterized by myofibrillar perturbations (FLNC), but human associated FILIP1 not yet described. Here, we report on five patients from four unrelated consanguineous families homozygous (two nonsense two missense). Functional studies indicated...
Abstract Dysfunctional RNA processing caused by genetic defects in enzymes has a profound impact on the nervous system, resulting neurodevelopmental conditions. We characterized recessive neurological disorder 18 children and young adults from 10 independent families typified intellectual disability, motor developmental delay gait disturbance. In some patients peripheral neuropathy, corpus callosum abnormalities progressive basal ganglia deposits were present. The is associated with rare...
Mutations in DLG3 are a rare cause of non‐syndromic X‐linked intellectual disability (XLID) (MRX90, OMIM *300189). Only ten mutations have been reported to date. The majority female heterozygous mutation carriers was healthy and had random X‐inactivation patterns. We report on an XLID family with novel mutation. 12‐year‐old male index patient moderate (ID) dysmorphic features. also present four relatives. A maternal aunt ID significantly skewed favorably inactivating the normal allele....
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...