4 results on '"van Beusekom, Ellen"'
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2. De Novo Mutations In Plxnd1 And Rev3L Cause Mobius Syndrome
- Author
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Tomas-Roca, Laura, Tsaalbi-Shtylik, Anastasia, Jansen, Jacob G., Singh, Manvendra K., Epstein, Jonathan A., Altunoglu, Umut, Verzijl, Harriette, Soria, Laura, van Beusekom, Ellen, Roscioli, Tony, Iqbal, Zafar, Gilissen, Christian, Hoischen, Alexander, de Brouwer, Arjan P. M., Erasmus, Corrie, Schubert, Dirk, Brunner, Han, Aytes, Antonio Perez, Marin, Faustino, and Aroca, Pilar
- Subjects
animal structures - Abstract
Mobius syndrome (MBS) is a neurological disorder that is characterized by paralysis of the facial nerves and variable other congenital anomalies. The aetiology of this syndrome has been enigmatic since the initial descriptions by von Graefe in 1880 and by Mobius in 1888, and it has been debated for decades whether MBS has a genetic or a non-genetic aetiology. Here, we report de novo mutations affecting two genes, PLXND1 and REV3L in MBS patients. PLXND1 and REV3L represent totally unrelated pathways involved in hindbrain development: neural migration and DNA translesion synthesis, essential for the replication of endogenously damaged DNA, respectively. Interestingly, analysis of Plxnd1 and Rev3l mutant mice shows that disruption of these separate pathways converge at the facial branchiomotor nucleus, affecting either motoneuron migration or proliferation. The finding that PLXND1 and REV3L mutations are responsible for a proportion of MBS patients suggests that de novo mutations in other genes might account for other MBS patients.
- Published
- 2015
3. De novo mutations in PLXND1 and REV3L cause Möbius syndrome
- Author
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Tony Roscioli, Arturo Carta, Jacob G. Jansen, Han G. Brunner, Christian Gilissen, Dirk Schubert, Zafar Iqbal, Manvendra K. Singh, Harriëtte T.F.M. Verzijl, Antonio Perez Aytes, Hülya Kayserili, George W. Padberg, Arjan P.M. de Brouwer, Faustino Marín, Pilar Aroca, Corrie E. Erasmus, Hans van Bokhoven, Umut Altunoglu, Laura Soria, Jonathan A. Epstein, Anastasia Tsaalbi-Shtylik, Ellen van Beusekom, Niels de Wind, Alexander Hoischen, Laura Tomás-Roca, Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, PO Box 9101, Nijmegen 6500 HB,The Netherlands., Department of Human Anatomy and Psychobiology, School of Medicine, University of Murcia, 30100 Espinardo (Murcia), Spain., Department of Human Genetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands., Department of Cell andDevelopmental Biology, Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, 9-105 SCTR, 3400 Civic Center Boulevard,Philadelphia, Pennsylvania 19104, USA, Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical SchoolSingapore, National Heart Center Singapore, 8 College Road, Singapore 169857, Singapore, Medical Genetics Department, Istanbul Medical Faculty,Istanbul University, Millet Caddesi, Capa, Fatih 34093, Turkey., Department of Neurology, Radboud University Medical Center, Donders Institute for Brain,Cognition and Behaviour, PO Box 9101, Nijmegen 6500 HB, The Netherlands., The Kinghorn Centre for Clinical Genomics, Garvan Institute of MedicalResearch, Sydney, New South Wales 2010, Australia, Department of Human Genetics, Radboud University Medical Center, Radboud Institute for MolecularLife Sciences (RIMLS), PO Box 9101, Nijmegen 6500 HB, The Netherlands., Department of Cognitive Neuroscience, Radboud University Medical Center,Donders Institute for Brain, Cognition and Behaviour, PO Box 9101, Nijmegen 6500 HB, The Netherlands, Department of Clinical Genetics, MaastrichtUniversity Medical Center, PO Box 5800, Maastricht 6200AZ, The Netherlands., Dysmorphology and Reproductive Genetics Unit, Moebius SyndromeFoundation of Spain, University Hospital LA FE, Valencia 46540, Spain., Ophthalmology Unit, Department of Biomedical, Biotechnological and TranslationalSciences (S.Bi.Bi.T.), University of Parma, via Gramsci 14, 43126, Parma, Italy, Karabey, Hülya Kayserili (ORCID 0000-0003-0376-499X & YÖK ID 7945), Tomas-Roca, Laura, Tsaalbi-Shtylik, Anastasia, Jansen, Jacob G., Singh, Manvendra K., Epstein, Jonathan A., Altunoglu, Umut, Verzijl, Harriette, Soria, Laura, van Beusekom, Ellen, Roscioli, Tony, Iqbal, Zafar, Gilissen, Christian, Hoischen, Alexander, de Brouwer,Arjan P. M., Erasmus, Corrie, Schubert, Dirk, Brunner, Han, Aytes, Antonio Perez, Marin, Faustino, Aroca, Pilar, Carta, Arturo, de Wind, Niels, Padberg, George W., van Bokhoven, Hans, School of Medicine, and Department of Medical Genetics
- Subjects
Möbius syndrome ,REV3L ,Heterozygote ,animal structures ,DNA damage ,Cell Adhesion Molecules, Neuronal ,Moebius syndrome ,Dna-damage ,Vascular etiology ,Syndrome variant ,Dutch family ,Gene ,Sequence ,Humans ,Cells ,Mechanisms ,Neurophysiology ,Other Research Donders Center for Medical Neuroscience [Radboudumc 0] ,General Physics and Astronomy ,Hindbrain ,DNA-Directed DNA Polymerase ,Biology ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Article ,Mice ,medicine ,Animals ,Exome ,PLXND1 ,Genetics ,Mutation ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,Multidisciplinary ,Membrane Glycoproteins ,Intracellular Signaling Peptides and Proteins ,Heterozygote advantage ,General Chemistry ,medicine.disease ,Mice, Mutant Strains ,Mobius Syndrome ,DNA-Binding Proteins ,Mobius syndrome ,Multidisciplinary sciences ,Molecular biology and genetics ,5 - Ciencias puras y naturales [CDU] ,DNA Damage - Abstract
Mobius syndrome (MBS) is a neurological disorder that is characterized by paralysis of the facial nerves and variable other congenital anomalies. The aetiology of this syndrome has been enigmatic since the initial descriptions by von Graefe in 1880 and by Mobius in 1888, and it has been debated for decades whether MBS has a genetic or a non-genetic aetiology. Here, we report de novo mutations affecting two genes, PLXND1 and REV3L in MBS patients. PLXND1 and REV3L represent totally unrelated pathways involved in hindbrain development: neural migration and DNA translesion synthesis, essential for the replication of endogenously damaged DNA, respectively. Interestingly, analysis of Plxnd1 and Rev3l mutant mice shows that disruption of these separate pathways converge at the facial branchiomotor nucleus, affecting either motoneuron migration or proliferation. The finding that PLXND1 and REV3L mutations are responsible for a proportion of MBS patients suggests that de novo mutations in other genes might account for other MBS patients., Fundacion Seneca fellowship; EMBO short-term fellowship; IBRO Project InEurope grants programme; Fundacion Cultural Privada Esteban-Romero; European Union FP7 Large-Scale Integrating Project Genetic and Epigenetic Networks in Cognitive Dysfunction; Scientific and Technological Research Council of Turkey (TÜBİTAK); CRANIRARE consortia of the European Research Area Network (E-RARE); Italian Association of Mobius Syndrome (AISMO); Dutch Cancer Society; Netherlands Organization for Health Research and Development
- Published
- 2015
4. Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice
- Author
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Kishan Sokhi, Jacqueline Ramsay, Tanya Bardakjian, Adele Schneider, Nursel Elcioglu, Raoul C.M. Hennekam, C. Nur Semerci, Ferda Ozkinay, Joe Rainger, David Sexton, Andrea Superti Furga, Anita Saponari, Lina Ramos, Ellen van Beusekom, Malcolm E. Fisher, Gabriele Gillessen-Kaesbach, Anita Wischmeijer, Ian J. Jackson, Sérgio B. Sousa, Hans van Bokhoven, Rainer Koenig, Lihadh Al-Gazali, Paul Perry, Peter Branney, Louise S. Bicknell, Harris Morrison, Livia Garavelli, Dagmar Wieczorek, André Mégarbané, Rosanna Pallotta, Han G. Brunner, Lisa McKie, Saemah Nuzhat Zafar, Philippe Gautier, Ayesha Khan, David R. FitzPatrick, ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, Paediatrics, Ege Üniversitesi, Rainger, Joe, van Beusekom, Ellen, Ramsay, Jacqueline K., McKie, Lisa, Al-Gazali, Lihadh, Pallotta, Rosanna, Saponari, Anita, Branney, Peter, Fisher, Malcolm, Morrison, Harris, Bicknell, Louise, Gautier, Philippe, Perry, Paul, Sokhi, Kishan, Sexton, David, Bardakjian, Tanya M., Schneider, Adele S., Elcioglu, Nursel, Ozkinay, Ferda, Koenig, Rainer, Megarbane, Andre, Semerci, C. Nur, Khan, Ayesha, Zafar, Saemah, Hennekam, Raoul, Sousa, Sergio B., Ramos, Lina, Garavelli, Livia, Furga, Andrea Superti, Wischmeijer, Anita, Jackson, Ian J., Gillessen-Kaesbach, Gabriele, Brunner, Han G., Wieczorek, Dagmar, van Bokhoven, Hans, FitzPatrick, David R., and Faculteit der Geneeskunde
- Subjects
ANOMALIES ,DNA Mutational Analysis ,PROTEIN ,anophthalmia ,gene targeting ,Bone Morphogenetic Protein 1 ,hindlimb ,Mice ,Xenopus laevis ,genetic linkage ,BINDING ,genetics ,Waardenburg's Syndrome ,Waardenburg Syndrome ,clinical article ,C57BL mouse ,adult ,Mus ,microsatellite marker ,DEFECTS ,gene expression regulation ,Disease gene identification ,BMP1 protein, human ,Pedigree ,Medicine ,down regulation ,mutational analysis ,drug antagonism ,medicine.medical_specialty ,SMOC1 protein, human ,embryo ,Bone morphogenetic protein ,animal tissue ,loss of function mutation ,Smoc1 gene ,Genetics ,Humans ,human ,Biology ,Molecular Biology ,Waardenburg syndrome ,mouse ,Ecology, Evolution, Behavior and Systematics ,MUTATIONS ,animal model ,Correction ,SMOC-1 protein, mouse ,school child ,medicine.disease ,Mice, Inbred C57BL ,Human Reproduction [NCEBP 12] ,gene function ,Endocrinology ,decapentaplegic protein ,Genetics and epigenetic pathways of disease Functional Neurogenomics [NCMLS 6] ,Mutation ,Cancer Research ,frameshift mutation ,Medizin ,nonsense mutation ,Gene Expression ,mouse mutant ,Eye ,Bmp1 protein, mouse ,Autosomal Recessive ,bone morphogenetic protein ,Missense mutation ,animal ,Osteonectin ,SPECIFICATION ,Genetics (clinical) ,RECESSIVE ANOPHTHALMIA ,limb ,cleft palate ,Mice, Knockout ,child ,Coloboma ,ABNORMALITIES ,messenger RNA ,article ,pedigree ,female ,Mammalia ,Models, Animal ,Drosophila ,Research Article ,gene locus ,lcsh:QH426-470 ,Nonsense mutation ,procollagen C proteinase ,male ,ddc:570 ,Internal medicine ,medicine ,Animalia ,Animals ,gene ,SMOC 1 protein, mouse ,gene identification ,growth, development and aging ,Clinical Genetics ,Phenocopy ,nonhuman ,Anophthalmia ,missense mutation ,syndactyly ,Anophthalmos ,nucleotide sequence ,Human Genetics ,Extremities ,infant ,lcsh:Genetics ,XENOPUS ,CELL-DEATH ,adolescent ,Genetics of Disease ,Syndactyly ,homozygosity ,Genetics and epigenetic pathways of disease Genomic disorders and inherited multi-system disorders [NCMLS 6] ,metabolism ,Animal Genetics - Abstract
WOS: 000293338600004, PubMed ID: 21750680, Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site-and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc(1tm1a)) that reduces mRNA to similar to 10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc(1tm1a/tm1a)). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc(1tm1a/tm1a) embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice., Medical Research Council (UK)Medical Research Council UK (MRC); Medical Research CouncilMedical Research Council UK (MRC) [MC_U127561093, MC_PC_U127561112, MC_U127561112], Funding for this project was provided as an intramural program grant from the Medical Research Council (UK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- Published
- 2011
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