A5062285975- Blood disorders and treatments
- Immunodeficiency and Autoimmune Disorders
- Cellular transport and secretion
- Hypertrophic osteoarthropathy and related conditions
- Erythrocyte Function and Pathophysiology
- Autoimmune Bullous Skin Diseases
- Dermatological and Skeletal Disorders
- Congenital limb and hand anomalies
- Neurofibromatosis and Schwannoma Cases
- Bone and Dental Protein Studies
- Genomic variations and chromosomal abnormalities
- Connective tissue disorders research
- Genetic and rare skin diseases.
- Acute Myeloid Leukemia Research
- Mitochondrial Function and Pathology
- Ion channel regulation and function
- Biomedical Research and Pathophysiology
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- Ion Transport and Channel Regulation
- Autoimmune and Inflammatory Disorders Research
- Peptidase Inhibition and Analysis
- Microtubule and mitosis dynamics
- Muscle Physiology and Disorders
- Congenital heart defects research
Charité - Universitätsmedizin Berlin
2009-2024
Humboldt-Universität zu Berlin
2024
Freie Universität Berlin
2008-2024
Max Delbrück Center
2004-2022
Molina Center for Energy and the Environment
2012
University of Cologne
2008-2011
Mental retardation affects 2-3% of the population and shows a high heritability. Neurodevelopmental disorders that include pronounced impairment in language speech skills occur less frequently. For most cases, molecular basis mental with or without disorder is unknown due to heterogeneity underlying genetic factors. We have used karyotyping on 1523 patients detect copy number variations (CNVs) including deletions duplications. These studies revealed three heterozygous overlapping solely...
Loss-of-function mutations in the gene COH1, also known as VPS13B, lead to autosomal recessive Cohen syndrome. However, cellular distribution and function of encoded protein COH1 (3997 amino acids), which lacks functional homologies other mammalian proteins, have remained enigmatic. We show here that is a peripheral Golgi membrane strongly co-localizes with cis-Golgi matrix GM130. Consistent its subcellular localization, depletion using RNAi causes fragmentation ribbon into ministacks....
Digital clubbing is usually secondary to different acquired diseases. Primary hypertrophic osteoarthropathy (PHO) a rare hereditary disorder with variable digital as the most prominent feature, subperiosteal new bone formation, and arthropathy. Recently, mutations in 15-hydroxy-prostaglandin dehydrogenase (15-PGDH) encoding gene HPGD were found cause PHO. Here, we identified three unrelated families prostaglandin transporter (PGT) SLCO2A1 which presumably result reduced metabolic clearance...
Cohen syndrome is characterised by mental retardation, postnatal microcephaly, facial dysmorphism, pigmentary retinopathy, myopia, and intermittent neutropenia. Mutations in COH1 (VPS13B) have been found patients with from diverse ethnic origins. We carried out mutation analysis twelve novel nine families. In this series, we identified 13 different mutations COH1, of these are including six frameshift mutations, four nonsense two splice site a one-codon deletion. Since transcripts reported...
Abstract Autosomal recessive Cohen syndrome is a neurodevelopmental disorder characterized by postnatal microcephaly, intellectual disability, and typical facial gestalt. Genetic variants in VPS13B have been found to cause syndrome, but also linked autism, retinal disease, primary immunodeficiency, short stature. While it well established that loss-of-function mutations of the relevance missense for pathomechanism remains unexplained. Here, we investigate their pathogenic effect through...
Bone fragility due to osteopenia, osteoporosis or debilitating focal skeletal dysplasias is a frequent observation in the Mendelian disease Neurofibromatosis type 1 (NF1). To determine mechanisms underlying bone NF1 we analyzed two conditional mouse models, Nf1Prx1 (limb knock-out) and Nf1Col1 (osteoblast specific knock-out), as well cortical samples from individuals with NF1. We examined tissue micro-computed tomography, qualitative quantitative histology, mechanical tensile analysis,...
Floating-Harbor syndrome is a rare autosomal dominant short stature with retarded speech development, intellectual disability and dysmorphic facial features. Recently mutations almost exclusively located in exon 34 of the Snf2-related CREBBP activator protein gene were identified to cause FHS. Here we report genetic analysis 5 patients fulfilling diagnostic criteria FHS obtained by Sanger sequencing. All them presented stature, delay as well psychomotor typical dysmorphism. Three showed good...
Acrodysostosis is characterized by a peripheral dysostosis that accompanied short stature, midface hypoplasia, and developmental delay. Recently, it was shown heterozygous point mutations in the PRKAR1A gene cause acrodysostosis with hormone resistance. By mutational analysis of we detected four different (p.Arg368Stop, p.Ala213Thr, p.Tyr373Cys, p.Arg335Cys) seven affected patients acrodysostosis. The combination clinical results, endocrinological parameters silico mutation gives evidence to...
The furosemide-sensitive Na+-K+-2Cl− cotransporter (NKCC2) is responsible for urine concentration and helps maintain systemic salt homeostasis. Its activity depends on trafficking to, insertion into, the apical membrane, as well phosphorylation of conserved N-terminal serine threonine residues. Vasopressin (AVP) signaling via PKA other kinases activates NKCC2. Association NKCC2 with lipid rafts facilitates its AVP-induced translocation activation at surface. Lipid raft microdomains typically...
Dominant or recessive mutations in the progressive ankylosis gene ANKH have been linked to familial chondrocalcinosis (CCAL2), craniometaphyseal dysplasia (CMD), mental retardation, deafness and syndrome (MRDA). The function of encoded membrane protein ANK cellular compartments other than plasma is unknown. Here, we show that localizes trans-Golgi network (TGN), clathrin-coated vesicles membrane. functionally interacts with clathrin associated adaptor (AP) complexes as loss either causes...
Primary hypertrophic osteoarthropathy (PHO), also known as pachydermoperiostosis, is a rare, multisystemic, autosomal recessive condition typically presenting with digital clubbing, osteoarthropathy, and various skin manifestations. Radiographs show distinctive periosteal reaction thickening along the long bones. PHO caused by homozygous mutations in <i>HPGD</i> gene chromosome 4q34.1 or <i>SLCO2A1</i> 3q22.1q22.2. Here, we report on 20-year-old male enlarged swollen...
Floating-Harbor syndrome is a rare autosomal dominant short stature with retarded speech development, intellectual disability and dysmorphic facial features. Recently mutations almost exclusively located in exon 34 of the Snf2-related CREBBP activator protein gene were identified to cause FHS. Here we report genetic analysis 5 patients fulfilling diagnostic criteria FHS obtained by Sanger sequencing. All them presented stature, delay as well psychomotor typical dysmorphism. Three showed good...
Cohen syndrome (CS) is an early-onset pediatric neurodevelopmental disorder characterized by postnatal microcephaly and intellectual disability. An accurate diagnosis for individuals with CS crucial, particularly their caretakers future prospects. predominantly caused rare homozygous or compound heterozygous pathogenic variants in the vacuolar protein sorting-associated 13B (
Mutations in COH1 (VPS13B) cause autosomal recessive Cohen syndrome, which is mainly characterized by mental retardation, progressive postnatal microcephaly, facial dysmorphism and retinopathy/myopia, intermittent neutropenia. Recently, our cell biological analysis identified as peripheral membrane protein of 3997 amino acids at the cytosolic site Golgi apparatus. Initial showed that loss upon RNAi impairs ability ribbon to (re)assemble thus induces fragmentation into mini‐stacks....
Patients with Neurofibromatosis Type 1 (NF1) develop subcutaneous benign tumors and dysfunction of multiple organs. About 30% NF1 patients are affected by skeletal manifestations such as osteopenia, kyphoscoliosis, tibia bowing, or pseudarthrosis the tibia. is caused autosomal dominant mutation gene encoding protein neurofibromin a regulator RAS/MAPK/ERK pathway. During last decade pre-clinical studies provided insights into molecular mechanisms associated phenotype. They also allowed...
Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)