Search

Your search keyword '"Van der Aa, Nathalie"' showing total 165 results
Start Over Author "Van der Aa, Nathalie"
165 results on '"Van der Aa, Nathalie"'

3. Author Correction: Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders

Author

Wang, Tianyun, Hoekzema, Kendra, Vecchio, Davide, Wu, Huidan, Sulovari, Arvis, Coe, Bradley P, Gillentine, Madelyn A, Wilfert, Amy B, Perez-Jurado, Luis A, Kvarnung, Malin, Sleyp, Yoeri, Earl, Rachel K, Rosenfeld, Jill A, Geisheker, Madeleine R, Han, Lin, Du, Bing, Barnett, Chris, Thompson, Elizabeth, Shaw, Marie, Carroll, Renee, Friend, Kathryn, Catford, Rachael, Palmer, Elizabeth E, Zou, Xiaobing, Ou, Jianjun, Li, Honghui, Guo, Hui, Gerdts, Jennifer, Avola, Emanuela, Calabrese, Giuseppe, Elia, Maurizio, Greco, Donatella, Lindstrand, Anna, Nordgren, Ann, Anderlid, Britt-Marie, Vandeweyer, Geert, Van Dijck, Anke, Van der Aa, Nathalie, McKenna, Brooke, Hancarova, Miroslava, Bendova, Sarka, Havlovicova, Marketa, Malerba, Giovanni, Bernardina, Bernardo Dalla, Muglia, Pierandrea, van Haeringen, Arie, Hoffer, Mariette JV, Franke, Barbara, Cappuccio, Gerarda, Delatycki, Martin, Lockhart, Paul J, Manning, Melanie A, Liu, Pengfei, Scheffer, Ingrid E, Brunetti-Pierri, Nicola, Rommelse, Nanda, Amaral, David G, Santen, Gijs WE, Trabetti, Elisabetta, Sedláček, Zdeněk, Michaelson, Jacob J, Pierce, Karen, Courchesne, Eric, Kooy, R Frank, Nordenskjöld, Magnus, Romano, Corrado, Peeters, Hilde, Bernier, Raphael A, Gecz, Jozef, Xia, Kun, and Eichler, Evan E

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Commerce, Management, Tourism and Services, SPARK Consortium
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

4. Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders

Author

Wang, Tianyun, Hoekzema, Kendra, Vecchio, Davide, Wu, Huidan, Sulovari, Arvis, Coe, Bradley P, Gillentine, Madelyn A, Wilfert, Amy B, Perez-Jurado, Luis A, Kvarnung, Malin, Sleyp, Yoeri, Earl, Rachel K, Rosenfeld, Jill A, Geisheker, Madeleine R, Han, Lin, Du, Bing, Barnett, Chris, Thompson, Elizabeth, Shaw, Marie, Carroll, Renee, Friend, Kathryn, Catford, Rachael, Palmer, Elizabeth E, Zou, Xiaobing, Ou, Jianjun, Li, Honghui, Guo, Hui, Gerdts, Jennifer, Avola, Emanuela, Calabrese, Giuseppe, Elia, Maurizio, Greco, Donatella, Lindstrand, Anna, Nordgren, Ann, Anderlid, Britt-Marie, Vandeweyer, Geert, Van Dijck, Anke, Van der Aa, Nathalie, McKenna, Brooke, Hancarova, Miroslava, Bendova, Sarka, Havlovicova, Marketa, Malerba, Giovanni, Bernardina, Bernardo Dalla, Muglia, Pierandrea, van Haeringen, Arie, Hoffer, Mariette JV, Franke, Barbara, Cappuccio, Gerarda, Delatycki, Martin, Lockhart, Paul J, Manning, Melanie A, Liu, Pengfei, Scheffer, Ingrid E, Brunetti-Pierri, Nicola, Rommelse, Nanda, Amaral, David G, Santen, Gijs WE, Trabetti, Elisabetta, Sedláček, Zdeněk, Michaelson, Jacob J, Pierce, Karen, Courchesne, Eric, Kooy, R Frank, Nordenskjöld, Magnus, Romano, Corrado, Peeters, Hilde, Bernier, Raphael A, Gecz, Jozef, Xia, Kun, and Eichler, Evan E

Subjects
Genetics, Prevention, 2.1 Biological and endogenous factors, Aetiology, Basic Helix-Loop-Helix Transcription Factors, CCCTC-Binding Factor, Case-Control Studies, Cohort Studies, DNA Mutational Analysis, DNA-Binding Proteins, Female, Genetic Association Studies, Genetic Predisposition to Disease, Heterogeneous-Nuclear Ribonucleoprotein U, High-Throughput Nucleotide Sequencing, Humans, KCNQ3 Potassium Channel, Male, Mutation, Neurodevelopmental Disorders, RNA-Binding Proteins, Repressor Proteins, Transcription Factors, SPARK Consortium
Abstract

Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case-control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF

Published
2020

5. Tracing the invisible mutant ADNP protein in Helsmoortel-Van der Aa syndrome patients.

Author

D'Incal, Claudio Peter, Cappuyns, Elisa, Choukri, Kaoutar, De Man, Kevin, Szrama, Kristy, Konings, Anthony, Bastini, Lina, Van Meel, Kim, Buys, Amber, Gabriele, Michele, Rizzuti, Ludovico, Vitriolo, Alessandro, Testa, Giuseppe, Mohn, Fabio, Bühler, Marc, Van der Aa, Nathalie, Van Dijck, Anke, Kooy, R. Frank, and Berghe, Wim Vanden

Subjects
MUTANT proteins, LYMPHOBLASTOID cell lines, PEPTIDES, ESCHERICHIA coli, BINDING site assay, ENDONUCLEASES, IMMUNOGLOBULINS
Abstract

Heterozygous de novo mutations in the Activity-Dependent Neuroprotective Homeobox (ADNP) gene underlie Helsmoortel-Van der Aa syndrome (HVDAS). Most of these mutations are situated in the last exon and we previously demonstrated escape from nonsense-mediated decay by detecting mutant ADNP mRNA in patient blood. In this study, wild-type and ADNP mutants are investigated at the protein level and therefore optimal detection of the protein is required. Detection of ADNP by means of western blotting has been ambiguous with reported antibodies resulting in non-specific bands without unique ADNP signal. Validation of an N-terminal ADNP antibody (Aviva Systems) using a blocking peptide competition assay allowed to differentiate between specific and non-specific signals in different sample materials, resulting in a unique band signal around 150 kDa for ADNP, above its theoretical molecular weight of 124 kDa. Detection with different C-terminal antibodies confirmed the signals at an observed molecular weight of 150 kDa. Our antibody panel was subsequently tested by immunoblotting, comparing parental and homozygous CRISPR/Cas9 endonuclease-mediated Adnp knockout cell lines and showed disappearance of the 150 kDa signal, indicative for intact ADNP. By means of both a GFPSpark and Flag-tag N-terminally fused to a human ADNP expression vector, we detected wild-type ADNP together with mutant forms after introduction of patient mutations in E. coli expression systems by site-directed mutagenesis. Furthermore, we were also able to visualize endogenous ADNP with our C-terminal antibody panel in heterozygous cell lines carrying ADNP patient mutations, while the truncated ADNP mutants could only be detected with epitope-tag-specific antibodies, suggesting that addition of an epitope-tag possibly helps stabilizing the protein. However, western blotting of patient-derived hiPSCs, immortalized lymphoblastoid cell lines and post-mortem patient brain material failed to detect a native mutant ADNP protein. In addition, an N-terminal immunoprecipitation-competent ADNP antibody enriched truncating mutants in overexpression lysates, whereas implementation of the same method failed to enrich a possible native mutant protein in immortalized patient-derived lymphoblastoid cell lines. This study aims to shape awareness for critical assessment of mutant ADNP protein analysis in Helsmoortel-Van der Aa syndrome. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

7. The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

Author

Koolen, David A, Pfundt, Rolph, Linda, Katrin, Beunders, Gea, Veenstra-Knol, Hermine E, Conta, Jessie H, Fortuna, Ana Maria, Gillessen-Kaesbach, Gabriele, Dugan, Sarah, Halbach, Sara, Abdul-Rahman, Omar A, Winesett, Heather M, Chung, Wendy K, Dalton, Marguerite, Dimova, Petia S, Mattina, Teresa, Prescott, Katrina, Zhang, Hui Z, Saal, Howard M, Hehir-Kwa, Jayne Y, Willemsen, Marjolein H, Ockeloen, Charlotte W, Jongmans, Marjolijn C, Van der Aa, Nathalie, Failla, Pinella, Barone, Concetta, Avola, Emanuela, Brooks, Alice S, Kant, Sarina G, Gerkes, Erica H, Firth, Helen V, Õunap, Katrin, Bird, Lynne M, Masser-Frye, Diane, Friedman, Jennifer R, Sokunbi, Modupe A, Dixit, Abhijit, Splitt, Miranda, Kukolich, Mary K, McGaughran, Julie, Coe, Bradley P, Flórez, Jesús, Nadif Kasri, Nael, Brunner, Han G, Thompson, Elizabeth M, Gecz, Jozef, Romano, Corrado, Eichler, Evan E, and de Vries, Bert BA

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Rare Diseases, Pediatric, Neurosciences, Congenital Structural Anomalies, Brain Disorders, Clinical Research, Intellectual and Developmental Disabilities (IDD), Aetiology, 2.1 Biological and endogenous factors, Congenital, Abnormalities, Multiple, Adolescent, Adult, Child, Chromosome Deletion, Chromosomes, Human, Pair 17, Female, Humans, Intellectual Disability, Male, Middle Aged, Nuclear Proteins, Phenotype, Polymorphism, Single Nucleotide, DDD Study, Clinical Sciences, Genetics & Heredity, Clinical sciences
Abstract

The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Expressive language development is particularly impaired compared with receptive language or motor skills. Other frequently reported features include social and friendly behaviour, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies. The syndrome is caused by a truncating variant in the KAT8 regulatory NSL complex unit 1 (KANSL1) gene or by a 17q21.31 microdeletion encompassing KANSL1. Herein we describe a novel cohort of 45 individuals with KdVS of whom 33 have a 17q21.31 microdeletion and 12 a single-nucleotide variant (SNV) in KANSL1 (19 males, 26 females; age range 7 months to 50 years). We provide guidance about the potential pitfalls in the laboratory testing and emphasise the challenges of KANSL1 variant calling and DNA copy number analysis in the complex 17q21.31 region. Moreover, we present detailed phenotypic information, including neuropsychological features, that contribute to the broad phenotypic spectrum of the syndrome. Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype.

Published
2016

8. Aberrant Function of the C-Terminal Tail of HIST1H1E Accelerates Cellular Senescence and Causes Premature Aging

Author

Flex, Elisabetta, Martinelli, Simone, Van Dijck, Anke, Ciolfi, Andrea, Cecchetti, Serena, Coluzzi, Elisa, Pannone, Luca, Andreoli, Cristina, Radio, Francesca Clementina, Pizzi, Simone, Carpentieri, Giovanna, Bruselles, Alessandro, Catanzaro, Giuseppina, Pedace, Lucia, Miele, Evelina, Carcarino, Elena, Ge, Xiaoyan, Chijiwa, Chieko, Lewis, M.E. Suzanne, Meuwissen, Marije, Kenis, Sandra, Van der Aa, Nathalie, Larson, Austin, Brown, Kathleen, Wasserstein, Melissa P., Skotko, Brian G., Begtrup, Amber, Person, Richard, Karayiorgou, Maria, Roos, J. Louw, Van Gassen, Koen L., Koopmans, Marije, Bijlsma, Emilia K., Santen, Gijs W.E., Barge-Schaapveld, Daniela Q.C.M., Ruivenkamp, Claudia A.L., Hoffer, Mariette J.V., Lalani, Seema R., Streff, Haley, Craigen, William J., Graham, Brett H., van den Elzen, Annette P.M., Kamphuis, Daan J., Õunap, Katrin, Reinson, Karit, Pajusalu, Sander, Wojcik, Monica H., Viberti, Clara, Di Gaetano, Cornelia, Bertini, Enrico, Petrucci, Simona, De Luca, Alessandro, Rota, Rossella, Ferretti, Elisabetta, Matullo, Giuseppe, Dallapiccola, Bruno, Sgura, Antonella, Walkiewicz, Magdalena, Kooy, R. Frank, and Tartaglia, Marco

Published
2019
Full Text
View/download PDF

9. Clinical Presentation of a Complex Neurodevelopmental Disorder Caused by Mutations in ADNP

Author

Bakshi, Madhura, Wilson, Meredith, Berman, Yemina, Dickson, Rebecca, Fransen, Erik, Helsmoortel, Céline, Van den Ende, Jenneke, Van der Aa, Nathalie, van de Wijdeven, Marina J., Rosenblum, Jessica, Monteiro, Fabíola, Kok, Fernando, Quercia, Nada, Bowdin, Sarah, Dyment, David, Chitayat, David, Alkhunaizi, Ebba, Boonen, Susanne E., Keren, Boris, Jacquette, Aurelia, Faivre, Laurence, Bezieau, Stephane, Isidor, Bertrand, Rieß, Angelika, Moog, Ute, Lynch, Sally Ann, McVeigh, Terri, Elpeleg, Orly, Smeland, Marie Falkenberg, Fannemel, Madeleine, van Haeringen, Arie, Maas, Saskia M., Veenstra-Knol, H.E., Schouten, Meyke, Willemsen, Marjolein H., Marcelis, Carlo L., Ockeloen, Charlotte, van der Burgt, Ineke, Feenstra, Ilse, van der Smagt, Jasper, Jezela-Stanek, Aleksandra, Krajewska-Walasek, Malgorzata, González-Lamuño, Domingo, Anderlid, Britt-Marie, Malmgren, Helena, Nordenskjöld, Magnus, Clement, Emma, Hurst, Jane, Metcalfe, Kay, Mansour, Sahar, Lachlan, Katherine, Clayton-Smith, Jill, Hendon, Laura G., Abdulrahman, Omar A., Morrow, Eric, McMillan, Clare, Gerdts, Jennifer, Peeden, Joseph, Schrier Vergano, Samantha A., Valentino, Caitlin, Chung, Wendy K., Ozmore, Jillian R., Bedrosian-Sermone, Sandra, Dennis, Anna, Treat, Kayla, Hughes, Susan Starling, Safina, Nicole, Le Pichon, Jean-Baptiste, McGuire, Marianne, Infante, Elena, Madan-Khetarpal, Suneeta, Desai, Sonal, Benke, Paul, Krokosky, Alyson, Cristian, Ingrid, Baker, Laura, Gripp, Karen, Stessman, Holly A., Eichenberger, Jacob, Jayakar, Parul, Pizzino, Amy, Manning, Melanie Ann, Slattery, Leah, Van Dijck, Anke, Vulto-van Silfhout, Anneke T., Cappuyns, Elisa, van der Werf, Ilse M., Mancini, Grazia M., Tzschach, Andreas, Bernier, Raphael, Gozes, Illana, Eichler, Evan E., Romano, Corrado, Lindstrand, Anna, Nordgren, Ann, Kvarnung, Malin, Kleefstra, Tjitske, de Vries, Bert B.A., Küry, Sébastien, Rosenfeld, Jill A., Meuwissen, Marije E., Vandeweyer, Geert, and Kooy, R. Frank

Published
2019
Full Text
View/download PDF

10. ADNP dysregulates methylation and mitochondrial gene expression in the cerebellum of a Helsmoortel–Van der Aa syndrome autopsy case.

Author

D'Incal, Claudio, Van Dijck, Anke, Ibrahim, Joe, De Man, Kevin, Bastini, Lina, Konings, Anthony, Elinck, Ellen, Gozes, lllana, Marusic, Zlatko, Anicic, Mirna, Vukovic, Jurica, Van der Aa, Nathalie, Mateiu, Ligia, Vanden Berghe, Wim, and Kooy, R. Frank

Subjects
AUTOPSY, GENE expression, TUBULINS, MITOCHONDRIA, CEREBELLUM, CARRIER proteins, IMMUNOPRECIPITATION, BRUGADA syndrome
Abstract

Background: Helsmoortel–Van der Aa syndrome is a neurodevelopmental disorder in which patients present with autism, intellectual disability, and frequent extra-neurological features such as feeding and gastrointestinal problems, visual impairments, and cardiac abnormalities. All patients exhibit heterozygous de novo nonsense or frameshift stop mutations in the Activity-Dependent Neuroprotective Protein (ADNP) gene, accounting for a prevalence of 0.2% of all autism cases worldwide. ADNP fulfills an essential chromatin remodeling function during brain development. In this study, we investigated the cerebellum of a died 6-year-old male patient with the c.1676dupA/p.His559Glnfs*3 ADNP mutation. Results: The clinical presentation of the patient was representative of the Helsmoortel–Van der Aa syndrome. During his lifespan, he underwent two liver transplantations after which the child died because of multiple organ failure. An autopsy was performed, and various tissue samples were taken for further analysis. We performed a molecular characterization of the cerebellum, a brain region involved in motor coordination, known for its highest ADNP expression and compared it to an age-matched control subject. Importantly, epigenome-wide analysis of the ADNP cerebellum identified CpG methylation differences and expression of multiple pathways causing neurodevelopmental delay. Interestingly, transcription factor motif enrichment analysis of differentially methylated genes showed that the ADNP binding motif was the most significantly enriched. RNA sequencing of the autopsy brain further identified downregulation of the WNT signaling pathway and autophagy defects as possible causes of neurodevelopmental delay. Ultimately, label-free quantification mass spectrometry identified differentially expressed proteins involved in mitochondrial stress and sirtuin signaling pathways amongst others. Protein–protein interaction analysis further revealed a network including chromatin remodelers (ADNP, SMARCC2, HDAC2 and YY1), autophagy-related proteins (LAMP1, BECN1 and LC3) as well as a key histone deacetylating enzyme SIRT1, involved in mitochondrial energy metabolism. The protein interaction of ADNP with SIRT1 was further biochemically validated through the microtubule-end binding proteins EB1/EB3 by direct co-immunoprecipitation in mouse cerebellum, suggesting important mito-epigenetic crosstalk between chromatin remodeling and mitochondrial energy metabolism linked to autophagy stress responses. This is further supported by mitochondrial activity assays and stainings in patient-derived fibroblasts which suggest mitochondrial dysfunctions in the ADNP deficient human brain. Conclusion: This study forms the baseline clinical and molecular characterization of an ADNP autopsy cerebellum, providing novel insights in the disease mechanisms of the Helsmoortel–Van der Aa syndrome. By combining multi-omic and biochemical approaches, we identified a novel SIRT1-EB1/EB3-ADNP protein complex which may contribute to autophagic flux alterations and impaired mitochondrial metabolism in the Helsmoortel–Van der Aa syndrome and holds promise as a new therapeutic target. Highlights: The ADNP patient mutation affects genome-wide methylation and leads to neurodevelopmental abnormalities. The ADNP brain transcriptome reveals impaired neuronal differentiation and cellular homeostasis by aberrant signaling of the WNT pathway and autophagy process. ADNP forms a complex with SIRT1 through the microtubule end-binding proteins EB1 and EB3. Mitochondrial gene expression is impaired in the ADNP brain and patient-derived cellular models. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

12. Implementation of genomic arrays in prenatal diagnosis: The Belgian approach to meet the challenges

Author

Vanakker, Olivier, Vilain, Catheline, Janssens, Katrien, Van der Aa, Nathalie, Smits, Guillaume, Bandelier, Claude, Blaumeiser, Bettina, Bulk, Saskia, Caberg, Jean-Hubert, De Leener, Anne, De Rademaeker, Marjan, de Ravel, Thomy, Desir, Julie, Destree, Anne, Dheedene, Annelies, Gaillez, Stéphane, Grisart, Bernard, Hellin, Ann-Cécile, Janssens, Sandra, Keymolen, Kathelijn, Menten, Björn, Pichon, Bruno, Ravoet, Marie, Revencu, Nicole, Rombout, Sonia, Staessens, Catherine, Van Den Bogaert, Ann, Van Den Bogaert, Kris, Vermeesch, Joris R., Kooy, Frank, Sznajer, Yves, and Devriendt, Koen

Published
2014
Full Text
View/download PDF

14. Clinical delineation of the PACS1-related syndrome—Report on 19 patients

Author

Schuurs-Hoeijmakers, Janneke H. M., Landsverk, Megan L., Foulds, Nicola, Kukolich, Mary K., Gavrilova, Ralitza H., Greville-Heygate, Stephanie, Hanson-Kahn, Andrea, Bernstein, Jonathan A., Glass, Jennifer, Chitayat, David, Burrow, Thomas A., Husami, Ammar, Collins, Kathleen, Wusik, Katie, van der Aa, Nathalie, Kooy, Frank, Brown, Kate Tatton, Gadzicki, Dorothea, Kini, Usha, Alvarez, Sara, Fernández-Jaén, Alberto, McGehee, Frank, Selby, Katherine, Tarailo-Graovac, Maja, Van Allen, Margot, van Karnebeek, Clara D. M., Stavropoulos, Dimitri J., Marshall, Christian R., Merico, Daniele, Gregor, Anne, Zweier, Christiane, Hopkin, Robert J., Chu, Yoyo Wing-Yiu, Chung, Brian Hon-Yin, de Vries, Bert B. A., Devriendt, Koenraad, Hurles, Matthew E., and Brunner, Han G.

Published
2016
Full Text
View/download PDF

15. Phenotypes and genotypes in non‐consanguineous and consanguineous primary microcephaly: High incidence of epilepsy

Author

Duerinckx, Sarah, primary, Désir, Julie, additional, Perazzolo, Camille, additional, Badoer, Cindy, additional, Jacquemin, Valérie, additional, Soblet, Julie, additional, Maystadt, Isabelle, additional, Tunca, Yusuf, additional, Blaumeiser, Bettina, additional, Ceulemans, Berten, additional, Courtens, Winnie, additional, Debray, François‐Guillaume, additional, Destree, Anne, additional, Devriendt, Koenraad, additional, Jansen, Anna, additional, Keymolen, Kathelijn, additional, Lederer, Damien, additional, Loeys, Bart, additional, Meuwissen, Marije, additional, Moortgat, Stéphanie, additional, Mortier, Geert, additional, Nassogne, Marie‐Cécile, additional, Sekhara, Tayeb, additional, Van Coster, Rudy, additional, Van Den Ende, Jenny, additional, Van der Aa, Nathalie, additional, Van Esch, Hilde, additional, Vanakker, Olivier, additional, Verhelst, Helene, additional, Vilain, Catheline, additional, Weckhuysen, Sarah, additional, Passemard, Sandrine, additional, Verloes, Alain, additional, Aeby, Alec, additional, Deconinck, Nicolas, additional, Van Bogaert, Patrick, additional, Pirson, Isabelle, additional, and Abramowicz, Marc, additional

Published
2021
Full Text
View/download PDF

18. Fourteen new cases contribute to the characterization of the 7q11.23 microduplication syndrome

Author

Van der Aa, Nathalie, Rooms, Liesbeth, Vandeweyer, Geert, van den Ende, Jenneke, Reyniers, Edwin, Fichera, Marco, Romano, Corrado, Delle Chiaie, Barbara, Mortier, Geert, Menten, Björn, Destrée, Anne, Maystadt, Isabelle, Männik, Katrin, Kurg, Ants, Reimand, Tiia, McMullan, Dom, Oley, Christine, Brueton, Louise, Bongers, Ernie M.H.F., van Bon, Bregje W.M., Pfund, Rolph, Jacquemont, Sebastien, Ferrarini, Alessandra, Martinet, Danielle, Schrander-Stumpel, Connie, Stegmann, Alexander P.A., Frints, Suzanna G.M., de Vries, Bert B.A., Ceulemans, Berten, and Kooy, R. Frank

Published
2009
Full Text
View/download PDF

20. Phenotypes and genotypes in non-consanguineous and consanguineous primary microcephaly: High incidence of epilepsy.

Author

UCL - (SLuc) Service de neurologie pédiatrique, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Centre de malformations vasculaires congénitales, UCL - (SLuc) Centre de référence en lésions congénitales de la moëlle épinière, UCL - (SLuc) Centre de référence pour l'épilepsie réfractaire, Duerinckx, Sarah, Désir, Julie, Perazzolo, Camille, Badoer, Cindy, Jacquemin, Valérie, Soblet, Julie, Maystadt, Isabelle, Tunca, Yusuf, Blaumeiser, Bettina, Ceulemans, Berten, Courtens, Winnie, Debray, François-Guillaume, Destree, Anne, Devriendt, Koenraad, Jansen, Anna, Keymolen, Kathelijn, Lederer, Damien, Loeys, Bart, Meuwissen, Marije, Moortgat, Stéphanie, Mortier, Geert, Nassogne, Marie-Cécile, Sekhara, Tayeb, Van Coster, Rudy, Van Den Ende, Jenny, Van der Aa, Nathalie, Van Esch, Hilde, Vanakker, Olivier, Verhelst, Helene, Vilain, Catheline, Weckhuysen, Sarah, Passemard, Sandrine, Verloes, Alain, Aeby, Alec, Deconinck, Nicolas, Van Bogaert, Patrick, Pirson, Isabelle, Abramowicz, Marc, UCL - (SLuc) Service de neurologie pédiatrique, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Centre de malformations vasculaires congénitales, UCL - (SLuc) Centre de référence en lésions congénitales de la moëlle épinière, UCL - (SLuc) Centre de référence pour l'épilepsie réfractaire, Duerinckx, Sarah, Désir, Julie, Perazzolo, Camille, Badoer, Cindy, Jacquemin, Valérie, Soblet, Julie, Maystadt, Isabelle, Tunca, Yusuf, Blaumeiser, Bettina, Ceulemans, Berten, Courtens, Winnie, Debray, François-Guillaume, Destree, Anne, Devriendt, Koenraad, Jansen, Anna, Keymolen, Kathelijn, Lederer, Damien, Loeys, Bart, Meuwissen, Marije, Moortgat, Stéphanie, Mortier, Geert, Nassogne, Marie-Cécile, Sekhara, Tayeb, Van Coster, Rudy, Van Den Ende, Jenny, Van der Aa, Nathalie, Van Esch, Hilde, Vanakker, Olivier, Verhelst, Helene, Vilain, Catheline, Weckhuysen, Sarah, Passemard, Sandrine, Verloes, Alain, Aeby, Alec, Deconinck, Nicolas, Van Bogaert, Patrick, Pirson, Isabelle, and Abramowicz, Marc

Abstract

Primary microcephaly (PM) is defined as a significant reduction in occipitofrontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge. We performed detailed phenotypic and genomic analyses in a large cohort (n = 169) of patients referred for PM and could establish a molecular diagnosis in 38 patients. Pathogenic variants in ASPM and WDR62 were the most frequent causes in non-consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in non-consanguineous patients (9%). Our series includes 11 novel pathogenic variants and we identify novel candidate genes including IGF2BP3 and DNAH2. We confirm the progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients with a molecular confirmation of the PM diagnosis, with various degrees of severity and seizure types. Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses, and improve the management of PM patients.

Published
2021

21. Phenotypes and genotypes in non-consanguineous and consanguineous primary microcephaly: High incidence of epilepsy

Author

Duerinckx, Sarah, Désir, Julie, Perazzolo, Camille, Badoer, Cindy, Jacquemin, Valérie, Soblet, Julie, Maystadt, Isabelle, Tunca, Yusuf, Blaumeiser, Bettina, Ceulemans, Berten, Courtens, Winnie, Debray, Francois-Guillaume, Donckier De Donceel, Annette, Devriendt, Koenraad, Jansen, Anna C M A.C., Keymolen, Kathelijn, Lederer, Damien, Loeys, Bart, Meuwissen, Marije E C, Moortgat, Stephanie, Mortier, Geert, Nassogne, Marie-Cécile, Sekhara, Tayeb, Van Coster, Rudy, Van Den Ende, Jenny, Van Der Aa, Nathalie, Van Esch, Hilde, Vanakker, Olivier, Verhelst, Hélène, Vilain, Catheline, Weckhuysen, Sarah, Passemard, Sandrine, Verloes, Alain, Aeby, Alec, Deconinck, Nicolas, Van Bogaert, Patrick, Pirson, Isabelle, Abramowicz, Marc, Duerinckx, Sarah, Désir, Julie, Perazzolo, Camille, Badoer, Cindy, Jacquemin, Valérie, Soblet, Julie, Maystadt, Isabelle, Tunca, Yusuf, Blaumeiser, Bettina, Ceulemans, Berten, Courtens, Winnie, Debray, Francois-Guillaume, Donckier De Donceel, Annette, Devriendt, Koenraad, Jansen, Anna C M A.C., Keymolen, Kathelijn, Lederer, Damien, Loeys, Bart, Meuwissen, Marije E C, Moortgat, Stephanie, Mortier, Geert, Nassogne, Marie-Cécile, Sekhara, Tayeb, Van Coster, Rudy, Van Den Ende, Jenny, Van Der Aa, Nathalie, Van Esch, Hilde, Vanakker, Olivier, Verhelst, Hélène, Vilain, Catheline, Weckhuysen, Sarah, Passemard, Sandrine, Verloes, Alain, Aeby, Alec, Deconinck, Nicolas, Van Bogaert, Patrick, Pirson, Isabelle, and Abramowicz, Marc

Abstract

Background: Primary microcephaly (PM) is defined as a significant reduction in occipitofrontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge. Methods: We performed detailed phenotypic and genomic analyses in a large cohort (n = 169) of patients referred for PM and could establish a molecular diagnosis in 38 patients. Results: Pathogenic variants in ASPM and WDR62 were the most frequent causes in non-consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in non-consanguineous patients (9%). Our series includes 11 novel pathogenic variants and we identify novel candidate genes including IGF2BP3 and DNAH2. We confirm the progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients with a molecular confirmation of the PM diagnosis, with various degrees of severity and seizure types. Conclusion: Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses, and improve the management of PM patients., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2021

22. The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism

Author

Vandeweyer, Geert, Helsmoortel, Céline, Van Dijck, Anke, Vulto-van Silfhout, Anneke T., Coe, Bradley P., Bernier, Raphael, Gerdts, Jennifer, Rooms, Liesbeth, van den Ende, Jenneke, Bakshi, Madhura, Wilson, Meredith, Nordgren, Ann, Hendon, Laura G., Abdulrahman, Omar A., Romano, Corrado, de Vries, Bert B.A., Kleefstra, Tjitske, Eichler, Evan E., Van der Aa, Nathalie, and Kooy, Frank R.

Published
2014
Full Text
View/download PDF

24. Homozygous and heterozygous disruptions of ANK3

Author

Iqbal, Zafar, Vandeweyer, Geert, van der Voet, Monique, Waryah, Ali Muhammad, Zahoor, Muhammad Yasir, Besseling, Judith A., Roca, Laura Tomas, Vulto-van Silfhout, Anneke T., Nijhof, Bonnie, Kramer, Jamie M., Van der Aa, Nathalie, Ansar, Muhammad, Peeters, Hilde, Helsmoortel, Céline, Gilissen, Christian, Vissers, Lisenka E.L.M., Veltman, Joris A., de Brouwer, Arjan P.M., Frank Kooy, R., Riazuddin, Sheikh, Schenck, Annette, van Bokhoven, Hans, and Rooms, Liesbeth

Published
2013
Full Text
View/download PDF

26. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus

Author

Jacquemont, Sébastien, Reymond, Alexandre, Zufferey, Flore, Harewood, Louise, Walters, Robin G., Kutalik, Zoltán, Martinet, Danielle, Shen, Yiping, Valsesia, Armand, Beckmann, Noam D., Thorleifsson, Gudmar, Belfiore, Marco, Bouquillon, Sonia, Campion, Dominique, de Leeuw, Nicole, de Vries, Bert B. A., Esko, Tõnu, Fernandez, Bridget A., Fernández-Aranda, Fernando, Fernández-Real, José Manuel, Gratacòs, Mònica, Guilmatre, Audrey, Hoyer, Juliane, Jarvelin, Marjo-Riitta, Kooy, Frank R., Kurg, Ants, Le Caignec, Cédric, Männik, Katrin, Platt, Orah S., Sanlaville, Damien, Van Haelst, Mieke M., Gomez, Sergi Villatoro, Walha, Faida, Wu, Bai-lin, Yu, Yongguo, Aboura, Azzedine, Addor, Marie-Claude, Alembik, Yves, Antonarakis, Stylianos E., Arveiler, Benoît, Barth, Magalie, Bednarek, Nathalie, Béna, Frédérique, Bergmann, Sven, Beri, Mylène, Bernardini, Laura, Blaumeiser, Bettina, Bonneau, Dominique, Bottani, Armand, Boute, Odile, Brunner, Han G., Cailley, Dorothée, Callier, Patrick, Chiesa, Jean, Chrast, Jacqueline, Coin, Lachlan, Coutton, Charles, Cuisset, Jean-Marie, Cuvellier, Jean-Christophe, David, Albert, de Freminville, Bénédicte, Delobel, Bruno, Delrue, Marie-Ange, Demeer, Bénédicte, Descamps, Dominique, Didelot, Gérard, Dieterich, Klaus, Disciglio, Vittoria, Doco-Fenzy, Martine, Drunat, Séverine, Duban-Bedu, Bénédicte, Dubourg, Christèle, Moustafa, Julia S. El-Sayed, Elliott, Paul, Faas, Brigitte H. W., Faivre, Laurence, Faudet, Anne, Fellmann, Florence, Ferrarini, Alessandra, Fisher, Richard, Flori, Elisabeth, Forer, Lukas, Gaillard, Dominique, Gerard, Marion, Gieger, Christian, Gimelli, Stefania, Gimelli, Giorgio, Grabe, Hans J., Guichet, Agnès, Guillin, Olivier, Hartikainen, Anna-Liisa, Heron, Délphine, Hippolyte, Loyse, Holder, Muriel, Homuth, Georg, Isidor, Bertrand, Jaillard, Sylvie, Jaros, Zdenek, Jiménez-Murcia, Susana, Helas, Géraldine Joly, Jonveaux, Philippe, Kaksonen, Satu, Keren, Boris, Kloss-Brandstätter, Anita, Knoers, Nine V. A. M., Koolen, David A., Kroisel, Peter M., Kronenberg, Florian, Labalme, Audrey, Landais, Emilie, Lapi, Elisabetta, Layet, Valérie, Legallic, Solenn, Leheup, Bruno, Leube, Barbara, Lewis, Suzanne, Lucas, Josette, MacDermot, Kay D., Magnusson, Pall, Marshall, Christian, Mathieu-Dramard, Michèle, McCarthy, Mark I., Meitinger, Thomas, Mencarelli, Maria Antonietta, Merla, Giuseppe, Moerman, Alexandre, Mooser, Vincent, Morice-Picard, Fanny, Mucciolo, Mafalda, Nauck, Matthias, Ndiaye, Ndeye Coumba, Nordgren, Ann, Pasquier, Laurent, Petit, Florence, Pfundt, Rolph, Plessis, Ghislaine, Rajcan-Separovic, Evica, Ramelli, Gian Paolo, Rauch, Anita, Ravazzolo, Roberto, Reis, Andre, Renieri, Alessandra, Richart, Cristobal, Ried, Janina S., Rieubland, Claudine, Roberts, Wendy, Roetzer, Katharina M., Rooryck, Caroline, Rossi, Massimiliano, Saemundsen, Evald, Satre, Véronique, Schurmann, Claudia, Sigurdsson, Engilbert, Stavropoulos, Dimitri J., Stefansson, Hreinn, Tengström, Carola, Thorsteinsdóttir, Unnur, Tinahones, Francisco J., Touraine, Renaud, Vallée, Louis, van Binsbergen, Ellen, Van der Aa, Nathalie, Vincent-Delorme, Catherine, Visvikis-Siest, Sophie, Vollenweider, Peter, Völzke, Henry, Vulto-van Silfhout, Anneke T., Waeber, Gérard, Wallgren-Pettersson, Carina, Witwicki, Robert M., Zwolinksi, Simon, Andrieux, Joris, Estivill, Xavier, Gusella, James F., Gustafsson, Omar, Metspalu, Andres, Scherer, Stephen W., Stefansson, Kari, Blakemore, Alexandra I. F., Beckmann, Jacques S., and Froguel, Philippe

Published
2011
Full Text
View/download PDF

28. Further molecular and clinical delineation of co-locating 17p13.3 microdeletions and microduplications that show distinctive phenotypes

Author

Bruno, Damien L, Anderlid, Britt-Marie, Lindstrand, Anna, van Ravenswaaij-Arts, Conny, Ganesamoorthy, Devika, Lundin, Johanna, Martin, Christa Lese, Douglas, Jessica, Nowak, Catherine, Adam, Margaret P, Kooy, R Frank, Van der Aa, Nathalie, Reyniers, Edwin, Vandeweyer, Geert, Stolte-Dijkstra, Irene, Dijkhuizen, Trijnie, Yeung, Alison, Delatycki, Martin, Borgström, Birgit, Thelin, Lena, Cardoso, Carlos, van Bon, Bregje, Pfundt, Rolph, de Vries, Bert B, Wallin, Anders, Amor, David J, James, Paul A, Slater, Howard R, and Schoumans, Jacqueline

Published
2010
Full Text
View/download PDF

29. Comprehensive Clinical and Molecular Assessment of 32 Probands With Congenital Contractural Arachnodactyly: Report of 14 Novel Mutations and Review of the Literature

Author

Callewaert, Bert L., Loeys, Bart L., Ficcadenti, Anna, Vermeer, Sascha, Landgren, Magnus, Kroes, Hester Y., Yaron, Yuval, Pope, Michael, Foulds, Nicola, Boute, Odile, Galán, Francisco, Kingston, Helen, Van der Aa, Nathalie, Salcedo, Iratxe, Swinkels, Marielle E., Wallgren-Pettersson, Carina, Gabrielli, Orazio, De Backer, Julie, Coucke, Paul J., and De Paepe, Anne M.

Published
2009
Full Text
View/download PDF

31. Clinical Presentation of a Complex Neurodevelopmental Disorder Caused by Mutations in ADNP

Author

Van Dijck, Anke, primary, Vulto-van Silfhout, Anneke T., additional, Cappuyns, Elisa, additional, van der Werf, Ilse M., additional, Mancini, Grazia M., additional, Tzschach, Andreas, additional, Bernier, Raphael, additional, Gozes, Illana, additional, Eichler, Evan E., additional, Romano, Corrado, additional, Lindstrand, Anna, additional, Nordgren, Ann, additional, Kvarnung, Malin, additional, Kleefstra, Tjitske, additional, de Vries, Bert B.A., additional, Küry, Sébastien, additional, Rosenfeld, Jill A., additional, Meuwissen, Marije E., additional, Vandeweyer, Geert, additional, Kooy, R. Frank, additional, Bakshi, Madhura, additional, Wilson, Meredith, additional, Berman, Yemina, additional, Dickson, Rebecca, additional, Fransen, Erik, additional, Helsmoortel, Céline, additional, Van den Ende, Jenneke, additional, Van der Aa, Nathalie, additional, van de Wijdeven, Marina J., additional, Rosenblum, Jessica, additional, Monteiro, Fabíola, additional, Kok, Fernando, additional, Quercia, Nada, additional, Bowdin, Sarah, additional, Dyment, David, additional, Chitayat, David, additional, Alkhunaizi, Ebba, additional, Boonen, Susanne E., additional, Keren, Boris, additional, Jacquette, Aurelia, additional, Faivre, Laurence, additional, Bezieau, Stephane, additional, Isidor, Bertrand, additional, Rieß, Angelika, additional, Moog, Ute, additional, Lynch, Sally Ann, additional, McVeigh, Terri, additional, Elpeleg, Orly, additional, Smeland, Marie Falkenberg, additional, Fannemel, Madeleine, additional, van Haeringen, Arie, additional, Maas, Saskia M., additional, Veenstra-Knol, H.E., additional, Schouten, Meyke, additional, Willemsen, Marjolein H., additional, Marcelis, Carlo L., additional, Ockeloen, Charlotte, additional, van der Burgt, Ineke, additional, Feenstra, Ilse, additional, van der Smagt, Jasper, additional, Jezela-Stanek, Aleksandra, additional, Krajewska-Walasek, Malgorzata, additional, González-Lamuño, Domingo, additional, Anderlid, Britt-Marie, additional, Malmgren, Helena, additional, Nordenskjöld, Magnus, additional, Clement, Emma, additional, Hurst, Jane, additional, Metcalfe, Kay, additional, Mansour, Sahar, additional, Lachlan, Katherine, additional, Clayton-Smith, Jill, additional, Hendon, Laura G., additional, Abdulrahman, Omar A., additional, Morrow, Eric, additional, McMillan, Clare, additional, Gerdts, Jennifer, additional, Peeden, Joseph, additional, Schrier Vergano, Samantha A., additional, Valentino, Caitlin, additional, Chung, Wendy K., additional, Ozmore, Jillian R., additional, Bedrosian-Sermone, Sandra, additional, Dennis, Anna, additional, Treat, Kayla, additional, Hughes, Susan Starling, additional, Safina, Nicole, additional, Le Pichon, Jean-Baptiste, additional, McGuire, Marianne, additional, Infante, Elena, additional, Madan-Khetarpal, Suneeta, additional, Desai, Sonal, additional, Benke, Paul, additional, Krokosky, Alyson, additional, Cristian, Ingrid, additional, Baker, Laura, additional, Gripp, Karen, additional, Stessman, Holly A., additional, Eichenberger, Jacob, additional, Jayakar, Parul, additional, Pizzino, Amy, additional, Manning, Melanie Ann, additional, and Slattery, Leah, additional

Published
2019
Full Text
View/download PDF

33. Challenges and opportunities in the investigation of unexplained intellectual disability using family-based whole-exome sequencing

Author

Helsmoortel, Céline, Vandeweyer, Geert, Ordoukhanian, P., Van Nieuwerburgh, F., Van der Aa, Nathalie, and Kooy, Frank

Subjects
Human medicine
Abstract

Intellectual disability (ID), characterized by an intellectual performance of at least 2 SD (standard deviations) below average is a frequent, lifelong disorder with a prevalence of 2-3%. Today, only for at most half of patients a diagnosis is made. Knowing the cause of the ID is important for patients and their relatives, as it allows for appropriate medical care, prognosis on further development of the disorder, familial counselling or access to support groups. Whole-exome sequencing (WES) now offers the possibility to identify the genetic cause for patients for which all previously available genetic tests, including karyotyping, specific gene analysis, or microarray analysis did not reveal causative abnormalities. However, data analysis of WES experiments is challenging. Here we present an analysis workflow implementable in any laboratory, requiring no bioinformatics knowledge. We demonstrated its feasibility on a cohort of 10 patients, in which we found a conclusive diagnosis in 3 and a likely diagnosis in 2 more patients. Of the three conclusive diagnoses, one was a clinically suspected mutation missed by Sanger sequencing, and one was an atypical presentation of a known monogenic disorder, highlighting two essential strengths of WES-based diagnostics.

Published
2015

34. The Koolen-de Vries syndrome : A phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

Author

Koolen, David A., Pfundt, Rolph, Linda, Katrin, Beunders, Gea, Veenstra-Knol, Hermine E., Conta, Essie H., Fortuna, Ana Maria, Gillessen-Kaesbach, Gabriele, Dugan, Sarah, Halbach, Sara, Abdul-Rahman, Omar A., Winesett, Heather M., Chung, Wendy K., Dalton, Marguerite, Dimova, Petia S., Mattina, Teresa, Prescott, Katrina, Zhang, Hui Z., Saal, Howard M., Hehir-Kwa, Jayne Y., Willemsen, Marjolein H., Ockeloen, Charlotte W., Jongmans, Marjolijn C., Van Der Aa, Nathalie, Failla, Pinella, Barone, Concetta, Avola, Emanuela, Brooks, Alice S., Kant, Sarina G., Gerkes, Erica H., Firth, Helen V., Unap, Katrin, Bird, Lynne M., Masser-Frye, Diane, Friedman, Jennifer R., Sokunbi, Modupe A., Dixit, Abhijit, Splitt, Miranda, Kukolich, Mary K., McGaughran, Julie, Coe, Bradley P., Flórez, Jess, Nadif Kasr, Nael, Brunner, Han G., Thompson, Elizabeth M., Gecz, Jozef, Romano, Corrado, Eichler, Evan E., De Vries, Bert B A, Koolen, David A., Pfundt, Rolph, Linda, Katrin, Beunders, Gea, Veenstra-Knol, Hermine E., Conta, Essie H., Fortuna, Ana Maria, Gillessen-Kaesbach, Gabriele, Dugan, Sarah, Halbach, Sara, Abdul-Rahman, Omar A., Winesett, Heather M., Chung, Wendy K., Dalton, Marguerite, Dimova, Petia S., Mattina, Teresa, Prescott, Katrina, Zhang, Hui Z., Saal, Howard M., Hehir-Kwa, Jayne Y., Willemsen, Marjolein H., Ockeloen, Charlotte W., Jongmans, Marjolijn C., Van Der Aa, Nathalie, Failla, Pinella, Barone, Concetta, Avola, Emanuela, Brooks, Alice S., Kant, Sarina G., Gerkes, Erica H., Firth, Helen V., Unap, Katrin, Bird, Lynne M., Masser-Frye, Diane, Friedman, Jennifer R., Sokunbi, Modupe A., Dixit, Abhijit, Splitt, Miranda, Kukolich, Mary K., McGaughran, Julie, Coe, Bradley P., Flórez, Jess, Nadif Kasr, Nael, Brunner, Han G., Thompson, Elizabeth M., Gecz, Jozef, Romano, Corrado, Eichler, Evan E., and De Vries, Bert B A

Published
2016

35. The Koolen-de Vries syndrome: A phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

Author

Genetica Sectie Oncogenetica, Koolen, David A., Pfundt, Rolph, Linda, Katrin, Beunders, Gea, Veenstra-Knol, Hermine E., Conta, Essie H., Fortuna, Ana Maria, Gillessen-Kaesbach, Gabriele, Dugan, Sarah, Halbach, Sara, Abdul-Rahman, Omar A., Winesett, Heather M., Chung, Wendy K., Dalton, Marguerite, Dimova, Petia S., Mattina, Teresa, Prescott, Katrina, Zhang, Hui Z., Saal, Howard M., Hehir-Kwa, Jayne Y., Willemsen, Marjolein H., Ockeloen, Charlotte W., Jongmans, Marjolijn C., Van Der Aa, Nathalie, Failla, Pinella, Barone, Concetta, Avola, Emanuela, Brooks, Alice S., Kant, Sarina G., Gerkes, Erica H., Firth, Helen V., Unap, Katrin, Bird, Lynne M., Masser-Frye, Diane, Friedman, Jennifer R., Sokunbi, Modupe A., Dixit, Abhijit, Splitt, Miranda, Kukolich, Mary K., McGaughran, Julie, Coe, Bradley P., Flórez, Jess, Nadif Kasr, Nael, Brunner, Han G., Thompson, Elizabeth M., Gecz, Jozef, Romano, Corrado, Eichler, Evan E., De Vries, Bert B A, Genetica Sectie Oncogenetica, Koolen, David A., Pfundt, Rolph, Linda, Katrin, Beunders, Gea, Veenstra-Knol, Hermine E., Conta, Essie H., Fortuna, Ana Maria, Gillessen-Kaesbach, Gabriele, Dugan, Sarah, Halbach, Sara, Abdul-Rahman, Omar A., Winesett, Heather M., Chung, Wendy K., Dalton, Marguerite, Dimova, Petia S., Mattina, Teresa, Prescott, Katrina, Zhang, Hui Z., Saal, Howard M., Hehir-Kwa, Jayne Y., Willemsen, Marjolein H., Ockeloen, Charlotte W., Jongmans, Marjolijn C., Van Der Aa, Nathalie, Failla, Pinella, Barone, Concetta, Avola, Emanuela, Brooks, Alice S., Kant, Sarina G., Gerkes, Erica H., Firth, Helen V., Unap, Katrin, Bird, Lynne M., Masser-Frye, Diane, Friedman, Jennifer R., Sokunbi, Modupe A., Dixit, Abhijit, Splitt, Miranda, Kukolich, Mary K., McGaughran, Julie, Coe, Bradley P., Flórez, Jess, Nadif Kasr, Nael, Brunner, Han G., Thompson, Elizabeth M., Gecz, Jozef, Romano, Corrado, Eichler, Evan E., and De Vries, Bert B A

Published
2016

36. Myhre and LAPS syndromes: clinical and molecular review of 32 patients (vol 22, pg 1272, 2014)

Author

Michot, Caroline, Le Goff, Carine, Mahaut, Clementine, Afenjar, Alexandra, Brooks, Alice S., Campeau, Philippe M., Destree, Anne, Di Rocco, Maja, Donnai, Dian, Hennekam, Raoul, Heron, Delphine, Jacquemont, Sebastien, Kannu, Peter, Lin, Angela E., Manouvrier-Hanu, Sylvie, Mansour, Sahar, Marlin, Sandrine, McGowan, Ruth, Murphy, Helen, Raas-Rothschild, Annick, Rio, Marlene, Simon, Marleen, Stolte-Dijkstra, Irene, Stone, James R., Sznajer, Yves, Tolmie, John, Touraine, Renaud, van den Ende, Jenneke, van der Aa, Nathalie, van Essen, Ton, Verloes, Alain, Munnich, Arnold, Cormier-Daire, Valerie, Human Genetics, and Paediatric Genetics

Published
2014

39. Case 10476 : brachydactyly

Author

Huyskens, J., Vanhoenacker, Filip, Boutry, N., Parizel, Paul M., and Van der Aa, Nathalie

Subjects
Human medicine
Published
2012

40. Inborn oxidative phosphorylation defect as risk factor for propofol infusion syndrome

Author

Vanlander, A.V., Jorens, Philippe, Smet, J., Verbrugghe, Walter, van den Eynden, Gert, Pauwels, Patrick, and Van der Aa, Nathalie

Subjects
Human medicine
Abstract

Propofol is an anesthetic agent widely used for induction and maintenance of anesthesia, and sedation in children. Although generally considered as reliable and safe, administration of propofol can occasionally induce a potentially fatal complication known as propofol infusion syndrome (PRIS). Mitochondrial dysfunction has been implicated in the pathogenesis of PRIS. We report on an adult patient with Leber hereditary optic neuropathy (LHON) who developed PRIS. He was a carrier of the m.3460G>A mutation, one of the major three pathogenic point mutations associated with LHON. The propositus was blind and underwent propofol sedation after severe head injury. Five days after start of propofol infusion, the patient died. The activity of complex I of the oxidative phosphorylation (OXPHOS) system was severely deficient in skeletal muscle. Our observation indicates that fulminate PRIS can occur in an adult patient with an inborn OXPHOS defect and corroborates the hypothesis that PRIS is caused by inhibition of the OXPHOS system.

Published
2012

41. DOCK6Mutations Are Responsible for a Distinct Autosomal-Recessive Variant of Adams-Oliver Syndrome Associated with Brain and Eye Anomalies

Author

Sukalo, Maja, primary, Tilsen, Felix, additional, Kayserili, Hülya, additional, Müller, Dietmar, additional, Tüysüz, Beyhan, additional, Ruddy, Deborah M., additional, Wakeling, Emma, additional, Ørstavik, Karen Helene, additional, Bramswig, Nuria C., additional, Snape, Katie M., additional, Trembath, Richard, additional, De Smedt, Maryse, additional, van der Aa, Nathalie, additional, Skalej, Martin, additional, Mundlos, Stefan, additional, Wuyts, Wim, additional, Southgate, Laura, additional, and Zenker, Martin, additional

Published
2015
Full Text
View/download PDF

42. Positron Emission Tomography (PET) Quantification of GABAA Receptors in the Brain of Fragile X Patients

Author

D’Hulst, Charlotte, primary, Heulens, Inge, additional, Van der Aa, Nathalie, additional, Goffin, Karolien, additional, Koole, Michel, additional, Porke, Kathleen, additional, Van De Velde, Marc, additional, Rooms, Liesbeth, additional, Van Paesschen, Wim, additional, Van Esch, Hilde, additional, Van Laere, Koen, additional, and Kooy, R. Frank, additional

Published
2015
Full Text
View/download PDF

43. First de novo KCND3 mutation causes severe Kv4.3 channel dysfunction leading to early onset cerebellar ataxia, intellectual disability, oral apraxia and epilepsy

Author

Smets, Katrien, primary, Duarri, Anna, additional, Deconinck, Tine, additional, Ceulemans, Berten, additional, van de Warrenburg, Bart P., additional, Züchner, Stephan, additional, Gonzalez, Michael Anthony, additional, Schüle, Rebecca, additional, Synofzik, Matthis, additional, Van der Aa, Nathalie, additional, De Jonghe, Peter, additional, Verbeek, Dineke S., additional, and Baets, Jonathan, additional

Published
2015
Full Text
View/download PDF

45. A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP

Author

Helsmoortel, Celine, Vulto-van Silfhout, Anneke T., Coe, Bradley P., Vandeweyer, Geert, Rooms, Liesbeth, van den Ende, Jenneke, Schuurs-Hoeijmakers, Janneke H. M., Marcelis, Carlo L., Willemsen, Marjolein H., Vissers, Lisenka E. L. M., Yntema, Helger G., Bakshi, Madhura, Wilson, Meredith, Witherspoon, Kali T., Malmgren, Helena, Nordgren, Ann, Annerén, Göran, Fichera, Marco, Bosco, Paolo, Romano, Corrado, de Vries, Bert B. A., Kleefstra, Tjitske, Kooy, R. Frank, Eichler, Evan E., Van der Aa, Nathalie, Helsmoortel, Celine, Vulto-van Silfhout, Anneke T., Coe, Bradley P., Vandeweyer, Geert, Rooms, Liesbeth, van den Ende, Jenneke, Schuurs-Hoeijmakers, Janneke H. M., Marcelis, Carlo L., Willemsen, Marjolein H., Vissers, Lisenka E. L. M., Yntema, Helger G., Bakshi, Madhura, Wilson, Meredith, Witherspoon, Kali T., Malmgren, Helena, Nordgren, Ann, Annerén, Göran, Fichera, Marco, Bosco, Paolo, Romano, Corrado, de Vries, Bert B. A., Kleefstra, Tjitske, Kooy, R. Frank, Eichler, Evan E., and Van der Aa, Nathalie

Abstract

Despite the high heritability of autism spectrum disorders (ASD), characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests or activities(1), a genetic diagnosis can be established in only a minority of patients. Known genetic causes include chromosomal aberrations, such as the duplication of the 15q11-13 region, and monogenic causes, as in Rett and fragile- X syndromes. The genetic heterogeneity within ASD is striking, with even the most frequent causes responsible for only 1% of cases at the most. Even with the recent developments in nextgeneration sequencing, for the large majority of cases no molecular diagnosis can be established(2-7). Here, we report ten patients with ASD and other shared clinical characteristics, including intellectual disability and facial dysmorphisms caused by a mutation in ADNP, a transcription factor involved in the SWI/ SNF remodeling complex. We estimate this gene to be mutated in at least 0.17% of ASD cases, making it one of the most frequent ASD- associated genes known to date.

Published
2014
Full Text
View/download PDF

46. Implementation of genomic arrays in prenatal diagnosis: The Belgian approach to meet the challenges

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Centre de génétique médicale UCL, Vanakker, Olivier, Vilain, Catheline, Janssens, Katrien, Van der Aa, Nathalie, Smits, Guillaume, Bandelier, Claude, Blaumeiser, Bettina, Bulk, Saskia, Caberg, Jean-Hubert, De Leener, Anne, De Rademaeker, Marjan, de Ravel, Thomy, Desir, Julie, Destree, Anne, Dheedene, Annelies, Gaillez, Stéphane, Grisart, Bernard, Hellin, Ann-Cécile, Janssens, Sandra, Keymolen, Kathelijn, Menten, Björn, Pichon, Bruno, Ravoet, Marie, Revencu, Nicole, Rombout, Sonia, Staessens, Catherine, Van Den Bogaert, Ann, Van Den Bogaert, Kris, Vermeesch, Joris R., Kooy, Frank, Sznajer, Yves, Devriendt, Koen, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Centre de génétique médicale UCL, Vanakker, Olivier, Vilain, Catheline, Janssens, Katrien, Van der Aa, Nathalie, Smits, Guillaume, Bandelier, Claude, Blaumeiser, Bettina, Bulk, Saskia, Caberg, Jean-Hubert, De Leener, Anne, De Rademaeker, Marjan, de Ravel, Thomy, Desir, Julie, Destree, Anne, Dheedene, Annelies, Gaillez, Stéphane, Grisart, Bernard, Hellin, Ann-Cécile, Janssens, Sandra, Keymolen, Kathelijn, Menten, Björn, Pichon, Bruno, Ravoet, Marie, Revencu, Nicole, Rombout, Sonia, Staessens, Catherine, Van Den Bogaert, Ann, Van Den Bogaert, Kris, Vermeesch, Joris R., Kooy, Frank, Sznajer, Yves, and Devriendt, Koen

Abstract

After their successful introduction in postnatal testing, genome-wide arrays are now rapidly replacing conventional karyotyping in prenatal diagnostics. While previous studies have demonstrated the advantages of this method, we are confronted with difficulties regarding the technology and the ethical dilemmas inherent to genomic arrays. These include indication for testing, array design, interpretation of variants and how to deal with variants of unknown significance and incidental findings. The experiences with these issues reported in the literature are most often from single centres. Here, we report on a national consensus approach how microarray is implemented in all genetic centres in Belgium. These recommendations are subjected to constant re-evaluation based on our growing experience and can serve as a useful tool for those involved in prenatal diagnosis. © 2014 Elsevier Masson SAS.

Published
2014

47. Myhre and LAPS syndromes: Clinical and molecular review of 32 patients

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Centre de génétique médicale UCL, Michot, Caroline, Le Goff, Carine, Mahaut, Clémentine, Afenjar, Alexandra, Brooks, Alice S, Campeau, Philippe M., Destree, Anne, Di Rocco, Maja, Donnai, Dian, Hennekam, Raoul, Heron, Delphine, Jacquemont, Sébastien, Kannu, Peter, Lin, Angela E., Manouvrier-Hanu, Sylvie, Mansour, Sahar, Marlin, Sandrine, McGowan, Ruth, Murphy, Helen, Raas-Rothschild, Annick, Rio, Marlène, Simon, Marleen, Stolte-Dijkstra, Irene, Stone, James R, Sznajer, Yves, Tolmie, John, Touraine, Renaud, Van Den Ende, Jenneke, Van Der Aa, Nathalie, Van Essen, Ton, Verloes, Alain, Munnich, Arnold, Cormier-Daire, Valérie, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Centre de génétique médicale UCL, Michot, Caroline, Le Goff, Carine, Mahaut, Clémentine, Afenjar, Alexandra, Brooks, Alice S, Campeau, Philippe M., Destree, Anne, Di Rocco, Maja, Donnai, Dian, Hennekam, Raoul, Heron, Delphine, Jacquemont, Sébastien, Kannu, Peter, Lin, Angela E., Manouvrier-Hanu, Sylvie, Mansour, Sahar, Marlin, Sandrine, McGowan, Ruth, Murphy, Helen, Raas-Rothschild, Annick, Rio, Marlène, Simon, Marleen, Stolte-Dijkstra, Irene, Stone, James R, Sznajer, Yves, Tolmie, John, Touraine, Renaud, Van Den Ende, Jenneke, Van Der Aa, Nathalie, Van Essen, Ton, Verloes, Alain, Munnich, Arnold, and Cormier-Daire, Valérie

Abstract

Myhre syndrome is characterized by short stature, brachydactyly, facial features, pseudomuscular hypertrophy, joint limitation and hearing loss. We identified SMAD4 mutations as the cause of Myhre syndrome. SMAD4 mutations have also been identified in laryngotracheal stenosis, arthropathy, prognathism and short stature syndrome (LAPS). This study aimed to review the features of Myhre and LAPS patients to define the clinical spectrum of SMAD4 mutations. We included 17 females and 15 males ranging in age from 8 to 48 years. Thirty were diagnosed with Myhre syndrome and two with LAPS. SMAD4 coding sequence was analyzed by Sanger sequencing. Clinical and radiological features were collected from a questionnaire completed by the referring physicians. All patients displayed a typical facial gestalt, thickened skin, joint limitation and muscular pseudohypertrophy. Growth retardation was common (68.7%) and was variable in severity (from -5.5 to -2 SD), as was mild-to-moderate intellectual deficiency (87.5%) with additional behavioral problems in 56.2% of the patients. Significant health concerns like obesity, arterial hypertension, bronchopulmonary insufficiency, laryngotracheal stenosis, pericarditis and early death occurred in four. Twenty-nine patients had a de novo heterozygous SMAD4 mutation, including both patients with LAPS. In 27 cases mutation affected Ile500 and in two cases Arg496. The three patients without SMAD4 mutations had typical findings of Myhre syndrome. Myhre-LAPS syndrome is a clinically homogenous condition with life threatening complications in the course of the disease. Our identification of SMAD4 mutations in 29/32 cases confirms that SMAD4 is the major gene responsible for Myhre syndrome.

Published
2014

48. Mate pair sequencing for the detection of chromosomal aberrations in patients with intellectual disability and congenital malformations

Author

Vergult, Sarah, Van Binsbergen, Ellen, Sante, Tom, Nowak, Silke, Vanakker, Olivier, Claes, Kathleen, Poppe, Bruce, Van der Aa, Nathalie, van Roosmalen, Markus J, Duran, Karen, Tavakoli-Yaraki, Masoumeh, Swinkels, Marielle, van den Boogaard, Marie-José, van Haelst, Mieke, Roelens, Filip, Speleman, Frank, Cuppen, Edwin, Mortier, Geert, Kloosterman, Wigard P, Menten, Björn, Vergult, Sarah, Van Binsbergen, Ellen, Sante, Tom, Nowak, Silke, Vanakker, Olivier, Claes, Kathleen, Poppe, Bruce, Van der Aa, Nathalie, van Roosmalen, Markus J, Duran, Karen, Tavakoli-Yaraki, Masoumeh, Swinkels, Marielle, van den Boogaard, Marie-José, van Haelst, Mieke, Roelens, Filip, Speleman, Frank, Cuppen, Edwin, Mortier, Geert, Kloosterman, Wigard P, and Menten, Björn

Abstract

Recently, microarrays have replaced karyotyping as a first tier test in patients with idiopathic intellectual disability and/or multiple congenital abnormalities (ID/MCA) in many laboratories. Although in about 14-18% of such patients, DNA copy-number variants (CNVs) with clinical significance can be detected, microarrays have the disadvantage of missing balanced rearrangements, as well as providing no information about the genomic architecture of structural variants (SVs) like duplications and complex rearrangements. Such information could possibly lead to a better interpretation of the clinical significance of the SV. In this study, the clinical use of mate pair next-generation sequencing was evaluated for the detection and further characterization of structural variants within the genomes of 50 ID/MCA patients. Thirty of these patients carried a chromosomal aberration that was previously detected by array CGH or karyotyping and suspected to be pathogenic. In the remaining 20 patients no causal SVs were found and only benign aberrations were detected by conventional techniques. Combined cluster and coverage analysis of the mate pair data allowed precise breakpoint detection and further refinement of previously identified balanced and (complex) unbalanced aberrations, pinpointing the causal gene for some patients. We conclude that mate pair sequencing is a powerful technology that can provide rapid and unequivocal characterization of unbalanced and balanced SVs in patient genomes and can be essential for the clinical interpretation of some SVs.

Published
2014

50. Erratum: Myhre and LAPS syndromes: clinical and molecular review of 32 patients

Author

Michot, Caroline, primary, Le Goff, Carine, additional, Mahaut, Clémentine, additional, Afenjar, Alexandra, additional, Brooks, Alice S, additional, Campeau, Philippe M, additional, Destree, Anne, additional, Di Rocco, Maja, additional, Donnai, Dian, additional, Hennekam, Raoul, additional, Heron, Delphine, additional, Jacquemont, Sébastien, additional, Kannu, Peter, additional, Lin, Angela E, additional, Manouvrier-Hanu, Sylvie, additional, Mansour, Sahar, additional, Marlin, Sandrine, additional, McGowan, Ruth, additional, Murphy, Helen, additional, Raas-Rothschild, Annick, additional, Rio, Marléne, additional, Simon, Marleen, additional, Stolte-Dijkstra, Irene, additional, Stone, James R, additional, Sznajer, Yves, additional, Tolmie, John, additional, Touraine, Renaud, additional, van den Ende, Jenneke, additional, Van der Aa, Nathalie, additional, van Essen, Ton, additional, Verloes, Alain, additional, Munnich, Arnold, additional, and Cormier-Daire, Valérie, additional

Published
2014
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results