1,410 results on '"Brunner, Han G"'
Search Results
2. Genome sequencing as a generic diagnostic strategy for rare disease
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Schobers, Gaby, Derks, Ronny, den Ouden, Amber, Swinkels, Hilde, van Reeuwijk, Jeroen, Bosgoed, Ermanno, Lugtenberg, Dorien, Sun, Su Ming, Corominas Galbany, Jordi, Weiss, Marjan, Blok, Marinus J., Olde Keizer, Richelle A. C. M., Hofste, Tom, Hellebrekers, Debby, de Leeuw, Nicole, Stegmann, Alexander, Kamsteeg, Erik-Jan, Paulussen, Aimee D. C., Ligtenberg, Marjolijn J. L., Bradley, Xiangqun Zheng, Peden, John, Gutierrez, Alejandra, Pullen, Adam, Payne, Tom, Gilissen, Christian, van den Wijngaard, Arthur, Brunner, Han G., Nelen, Marcel, Yntema, Helger G., and Vissers, Lisenka E. L. M.
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- 2024
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3. Prevalence of chromosomal alterations in first-trimester spontaneous pregnancy loss
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Essers, Rick, Lebedev, Igor N., Kurg, Ants, Fonova, Elizaveta A., Stevens, Servi J. C., Koeck, Rebekka M., von Rango, Ulrike, Brandts, Lloyd, Deligiannis, Spyridon Panagiotis, Nikitina, Tatyana V., Sazhenova, Elena A., Tolmacheva, Ekaterina N., Kashevarova, Anna A., Fedotov, Dmitry A., Demeneva, Viktoria V., Zhigalina, Daria I., Drozdov, Gleb V., Al-Nasiry, Salwan, Macville, Merryn V. E., van den Wijngaard, Arthur, Dreesen, Jos, Paulussen, Aimee, Hoischen, Alexander, Brunner, Han G., Salumets, Andres, and Zamani Esteki, Masoud
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- 2023
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4. Phenotypic and mutational spectrum of ROR2‐related Robinow syndrome
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Lima, Ariadne R, Ferreira, Barbara M, Zhang, Chaofan, Jolly, Angad, Du, Haowei, White, Janson J, Dawood, Moez, Lins, Tulio C, Chiabai, Marcela A, Beusekom, Ellen, Cordoba, Mara S, Rosa, Erica CC Caldas, Kayserili, Hulya, Kimonis, Virginia, Wu, Erica, Mellado, Cecilia, Aggarwal, Vineet, Richieri‐Costa, Antonio, Brunoni, Décio, Canó, Talyta M, Jorge, Alexander AL, Kim, Chong A, Honjo, Rachel, Bertola, Débora R, Dandalo‐Girardi, Raissa M, Bayram, Yavuz, Gezdirici, Alper, Yilmaz‐Gulec, Elif, Gumus, Evren, Yilmaz, Gülay C, Okamoto, Nobuhiko, Ohashi, Hirofumi, Coban–Akdemir, Zeynep, Mitani, Tadahiro, Jhangiani, Shalini N, Muzny, Donna M, Regattieri, Neysa AP, Pogue, Robert, Pereira, Rinaldo W, Otto, Paulo A, Gibbs, Richard A, Ali, Bassam R, Bokhoven, Hans, Brunner, Han G, Sutton, V Reid, Lupski, James R, Vianna‐Morgante, Angela M, Carvalho, Claudia MB, and Mazzeu, Juliana F
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Clinical Research ,Pediatric ,Congenital Structural Anomalies ,Aetiology ,2.1 Biological and endogenous factors ,Craniofacial Abnormalities ,Dwarfism ,Genes ,Recessive ,Humans ,Limb Deformities ,Congenital ,Male ,Phenotype ,Receptor Tyrosine Kinase-like Orphan Receptors ,Urogenital Abnormalities ,chromosome microarray analysis ,craniofacial morphology ,exonic deletion ,HPO terms ,next-generation sequencing ,quantitative phenotyping cluster heatmap ,skeletal dysplasia ,WNT pathway ,Clinical Sciences ,Genetics & Heredity ,Clinical sciences - Abstract
Robinow syndrome is characterized by a triad of craniofacial dysmorphisms, disproportionate-limb short stature, and genital hypoplasia. A significant degree of phenotypic variability seems to correlate with different genes/loci. Disturbances of the noncanonical WNT-pathway have been identified as the main cause of the syndrome. Biallelic variants in ROR2 cause an autosomal recessive form of the syndrome with distinctive skeletal findings. Twenty-two patients with a clinical diagnosis of autosomal recessive Robinow syndrome were screened for variants in ROR2 using multiple molecular approaches. We identified 25 putatively pathogenic ROR2 variants, 16 novel, including single nucleotide variants and exonic deletions. Detailed phenotypic analyses revealed that all subjects presented with a prominent forehead, hypertelorism, short nose, abnormality of the nasal tip, brachydactyly, mesomelic limb shortening, short stature, and genital hypoplasia in male patients. A total of 19 clinical features were present in more than 75% of the subjects, thus pointing to an overall uniformity of the phenotype. Disease-causing variants in ROR2, contribute to a clinically recognizable autosomal recessive trait phenotype with multiple skeletal defects. A comprehensive quantitative clinical evaluation of this cohort delineated the phenotypic spectrum of ROR2-related Robinow syndrome. The identification of exonic deletion variant alleles further supports the contention of a loss-of-function mechanism in the etiology of the syndrome.
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- 2022
5. Comprehensive EHMT1 variants analysis broadens genotype-phenotype associations and molecular mechanisms in Kleefstra syndrome
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Rots, Dmitrijs, Bouman, Arianne, Yamada, Ayumi, Levy, Michael, Dingemans, Alexander J.M., de Vries, Bert B.A., Ruiterkamp-Versteeg, Martina, de Leeuw, Nicole, Ockeloen, Charlotte W., Pfundt, Rolph, de Boer, Elke, Kummeling, Joost, van Bon, Bregje, van Bokhoven, Hans, Kasri, Nael Nadif, Venselaar, Hanka, Alders, Marielle, Kerkhof, Jennifer, McConkey, Haley, Kuechler, Alma, Elffers, Bart, van Beeck Calkoen, Rixje, Hofman, Susanna, Smith, Audrey, Valenzuela, Maria Irene, Srivastava, Siddharth, Frazier, Zoe, Maystadt, Isabelle, Piscopo, Carmelo, Merla, Giuseppe, Balasubramanian, Meena, Santen, Gijs W.E., Metcalfe, Kay, Park, Soo-Mi, Pasquier, Laurent, Banka, Siddharth, Donnai, Dian, Weisberg, Daniel, Strobl-Wildemann, Gertrud, Wagemans, Annemieke, Vreeburg, Maaike, Baralle, Diana, Foulds, Nicola, Scurr, Ingrid, Brunetti-Pierri, Nicola, van Hagen, Johanna M., Bijlsma, Emilia K., Hakonen, Anna H., Courage, Carolina, Genevieve, David, Pinson, Lucile, Forzano, Francesca, Deshpande, Charu, Kluskens, Maria L., Welling, Lindsey, Plomp, Astrid S., Vanhoutte, Els K., Kalsner, Louisa, Hol, Janna A., Putoux, Audrey, Lazier, Johanna, Vasudevan, Pradeep, Ames, Elizabeth, O'Shea, Jessica, Lederer, Damien, Fleischer, Julie, O'Connor, Mary, Pauly, Melissa, Vasileiou, Georgia, Reis, André, Kiraly-Borri, Catherine, Bouman, Arjan, Barnett, Chris, Nezarati, Marjan, Borch, Lauren, Beunders, Gea, Özcan, Kübra, Miot, Stéphanie, Volker-Touw, Catharina M.L., van Gassen, Koen L.I., Cappuccio, Gerarda, Janssens, Katrien, Mor, Nofar, Shomer, Inna, Dominissini, Dan, Tedder, Matthew L., Muir, Alison M., Sadikovic, Bekim, Brunner, Han G., Vissers, Lisenka E.L.M., Shinkai, Yoichi, and Kleefstra, Tjitske
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- 2024
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6. Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes
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Rots, Dmitrijs, Choufani, Sanaa, Faundes, Victor, Dingemans, Alexander J.M., Joss, Shelagh, Foulds, Nicola, Jones, Elizabeth A., Stewart, Sarah, Vasudevan, Pradeep, Dabir, Tabib, Park, Soo-Mi, Jewell, Rosalyn, Brown, Natasha, Pais, Lynn, Jacquemont, Sébastien, Jizi, Khadijé, Ravenswaaij-Arts, Conny M.A. van, Kroes, Hester Y., Stumpel, Constance T.R. M., Ockeloen, Charlotte W., Diets, Illja J., Nizon, Mathilde, Vincent, Marie, Cogné, Benjamin, Besnard, Thomas, Kambouris, Marios, Anderson, Emily, Zackai, Elaine H., McDougall, Carey, Donoghue, Sarah, O'Donnell-Luria, Anne, Valivullah, Zaheer, O'Leary, Melanie, Srivastava, Siddharth, Byers, Heather, Leslie, Nancy, Mazzola, Sarah, Tiller, George E., Vera, Moin, Shen, Joseph J., Boles, Richard, Jain, Vani, Brischoux-Boucher, Elise, Kinning, Esther, Simpson, Brittany N., Giltay, Jacques C., Harris, Jacqueline, Keren, Boris, Guimier, Anne, Marijon, Pierre, Vries, Bert B.A. de, Motter, Constance S., Mendelsohn, Bryce A., Coffino, Samantha, Gerkes, Erica H., Afenjar, Alexandra, Visconti, Paola, Bacchelli, Elena, Maestrini, Elena, Delahaye-Duriez, Andree, Gooch, Catherine, Hendriks, Yvonne, Adams, Hieab, Thauvin-Robinet, Christel, Josephi-Taylor, Sarah, Bertoli, Marta, Parker, Michael J., Rutten, Julie W., Caluseriu, Oana, Vernon, Hilary J., Kaziyev, Jonah, Zhu, Jia, Kremen, Jessica, Frazier, Zoe, Osika, Hailey, Breault, David, Nair, Sreelata, Lewis, Suzanne M.E., Ceroni, Fabiola, Viggiano, Marta, Posar, Annio, Brittain, Helen, Giovanna, Traficante, Giulia, Gori, Quteineh, Lina, Ha-Vinh Leuchter, Russia, Zonneveld-Huijssoon, Evelien, Mellado, Cecilia, Marey, Isabelle, Coudert, Alicia, Aracena Alvarez, Mariana Inés, Kennis, Milou G.P., Bouman, Arianne, Roifman, Maian, Amorós Rodríguez, María Inmaculada, Ortigoza-Escobar, Juan Dario, Vernimmen, Vivian, Sinnema, Margje, Pfundt, Rolph, Brunner, Han G., Vissers, Lisenka E.L.M., Kleefstra, Tjitske, Weksberg, Rosanna, and Banka, Siddharth
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- 2024
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7. Diagnostic and prognostic relevance of using large gene panels in the genetic testing of patients with dilated cardiomyopathy
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Stroeks, Sophie L. V. M., Hellebrekers, Debby, Claes, Godelieve R. F., Krapels, Ingrid P. C., Henkens, Michiel H. T. M., Sikking, Maurits, Vanhoutte, Els K., Helderman-van den Enden, Apollonia, Brunner, Han G., van den Wijngaard, Arthur, and Verdonschot, Job A. J.
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- 2023
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8. Clonal Hematopoiesis Has Prognostic Value in Dilated Cardiomyopathy Independent of Age and Clone Size
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Sikking, Maurits A., Stroeks, Sophie L.V.M., Henkens, Michiel T.H.M., Raafs, Anne G., Cossins, Benjamin, van Deuren, Rosanne C., Steehouwer, Marlies, Riksen, Niels P., van den Wijngaard, Arthur, Brunner, Han G., Hoischen, Alexander, Verdonschot, Job A.J., and Heymans, Stephane R.B.
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- 2024
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9. Exploring uncertainties regarding unsolicited findings in genetic testing
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van der Schoot, Vyne, van der Meer, Eline, Hillen, Marij A., Yntema, Helger G., Brunner, Han G., and Oerlemans, Anke J.M.
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- 2024
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10. A recurrent de novo MAX p.Arg60Gln variant causes a syndromic overgrowth disorder through differential expression of c-Myc target genes
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Harris, Erica L., Roy, Vincent, Montagne, Martin, Rose, Ailsa M.S., Livesey, Helen, Reijnders, Margot R.F., Hobson, Emma, Sansbury, Francis H., Willemsen, Marjolein H., Pfundt, Rolph, Warren, Daniel, Long, Vernon, Carr, Ian M., Brunner, Han G., Sheridan, Eamonn G., Firth, Helen V., Lavigne, Pierre, and Poulter, James A.
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- 2024
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11. Left Atrial Function in Patients with Titin Cardiomyopathy
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HENKENS, MICHIEL T.H.M., RAAFS, ANNE G., VANLOON, TIM, VOS, JACQUELINE L., VANDENWIJNGAARD, ARTHUR, BRUNNER, HAN G., KRAPELS, INGRID P.C., KNACKSTEDT, CHRISTIAN, GERRETSEN, SUZANNE, HAZEBROEK, MARK R., VERNOOY, KEVIN, NIJVELDT, ROBIN, LUMENS, JOOST, and VERDONSCHOT, JOB A.J.
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- 2024
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12. Comprehensive de novo mutation discovery with HiFi long-read sequencing
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Kucuk, Erdi, van der Sanden, Bart P. G. H., O’Gorman, Luke, Kwint, Michael, Derks, Ronny, Wenger, Aaron M., Lambert, Christine, Chakraborty, Shreyasee, Baybayan, Primo, Rowell, William J., Brunner, Han G., Vissers, Lisenka E. L. M., Hoischen, Alexander, and Gilissen, Christian
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- 2023
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13. Truncating SRCAP variants outside the Floating-Harbor syndrome locus cause a distinct neurodevelopmental disorder with a specific DNA methylation signature
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Rots, Dmitrijs, Chater-Diehl, Eric, Dingemans, Alexander JM, Goodman, Sarah J, Siu, Michelle T, Cytrynbaum, Cheryl, Choufani, Sanaa, Hoang, Ny, Walker, Susan, Awamleh, Zain, Charkow, Joshua, Meyn, Stephen, Pfundt, Rolph, Rinne, Tuula, Gardeitchik, Thatjana, de Vries, Bert BA, Deden, A Chantal, Leenders, Erika, Kwint, Michael, Stumpel, Constance TRM, Stevens, Servi JC, Vermeulen, Jeroen R, van Harssel, Jeske VT, Bosch, Danielle GM, van Gassen, Koen LI, van Binsbergen, Ellen, de Geus, Christa M, Brackel, Hein, Hempel, Maja, Lessel, Davor, Denecke, Jonas, Slavotinek, Anne, Strober, Jonathan, Crunk, Amy, Folk, Leandra, Wentzensen, Ingrid M, Yang, Hui, Zou, Fanggeng, Millan, Francisca, Person, Richard, Xie, Yili, Liu, Shuxi, Ousager, Lilian B, Larsen, Martin, Schultz-Rogers, Laura, Morava, Eva, Klee, Eric W, Berry, Ian R, Campbell, Jennifer, Lindstrom, Kristin, Pruniski, Brianna, Neumeyer, Ann M, Radley, Jessica A, Phornphutkul, Chanika, Schmidt, Berkley, Wilson, William G, Õunap, Katrin, Reinson, Karit, Pajusalu, Sander, van Haeringen, Arie, Ruivenkamp, Claudia, Cuperus, Roos, Santos-Simarro, Fernando, Palomares-Bralo, María, Pacio-Míguez, Marta, Ritter, Alyssa, Bhoj, Elizabeth, Tønne, Elin, Tveten, Kristian, Cappuccio, Gerarda, Brunetti-Pierri, Nicola, Rowe, Leah, Bunn, Jason, Saenz, Margarita, Platzer, Konrad, Mertens, Mareike, Caluseriu, Oana, Nowaczyk, Małgorzata JM, Cohn, Ronald D, Kannu, Peter, Alkhunaizi, Ebba, Chitayat, David, Scherer, Stephen W, Brunner, Han G, Vissers, Lisenka ELM, Kleefstra, Tjitske, Koolen, David A, and Weksberg, Rosanna
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Genetics ,Clinical Research ,Brain Disorders ,Mental Health ,Intellectual and Developmental Disabilities (IDD) ,Aetiology ,2.1 Biological and endogenous factors ,Abnormalities ,Multiple ,Adenosine Triphosphatases ,Case-Control Studies ,Cohort Studies ,Craniofacial Abnormalities ,DNA Methylation ,Epigenesis ,Genetic ,Female ,Genetic Predisposition to Disease ,Growth Disorders ,Heart Septal Defects ,Ventricular ,Humans ,Infant ,Newborn ,Male ,Mutation ,Neurodevelopmental Disorders ,Phenotype ,DNA methylation signature ,Floating-Harbor syndrome ,SRCAP ,epigenomics ,genotype-phenotype correlation ,intellectual disability ,neurodevelopmental disorders ,non-FLHS SRCAP-related NDD ,nonsense-mediated decay ,speech delay ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Truncating variants in exons 33 and 34 of the SNF2-related CREBBP activator protein (SRCAP) gene cause the neurodevelopmental disorder (NDD) Floating-Harbor syndrome (FLHS), characterized by short stature, speech delay, and facial dysmorphism. Here, we present a cohort of 33 individuals with clinical features distinct from FLHS and truncating (mostly de novo) SRCAP variants either proximal (n = 28) or distal (n = 5) to the FLHS locus. Detailed clinical characterization of the proximal SRCAP individuals identified shared characteristics: developmental delay with or without intellectual disability, behavioral and psychiatric problems, non-specific facial features, musculoskeletal issues, and hypotonia. Because FLHS is known to be associated with a unique set of DNA methylation (DNAm) changes in blood, a DNAm signature, we investigated whether there was a distinct signature associated with our affected individuals. A machine-learning model, based on the FLHS DNAm signature, negatively classified all our tested subjects. Comparing proximal variants with typically developing controls, we identified a DNAm signature distinct from the FLHS signature. Based on the DNAm and clinical data, we refer to the condition as "non-FLHS SRCAP-related NDD." All five distal variants classified negatively using the FLHS DNAm model while two classified positively using the proximal model. This suggests divergent pathogenicity of these variants, though clinically the distal group presented with NDD, similar to the proximal SRCAP group. In summary, for SRCAP, there is a clear relationship between variant location, DNAm profile, and clinical phenotype. These results highlight the power of combined epigenetic, molecular, and clinical studies to identify and characterize genotype-epigenotype-phenotype correlations.
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- 2021
14. The performance of genome sequencing as a first-tier test for neurodevelopmental disorders
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van der Sanden, Bart P. G. H., Schobers, Gaby, Corominas Galbany, Jordi, Koolen, David A., Sinnema, Margje, van Reeuwijk, Jeroen, Stumpel, Connie T. R. M., Kleefstra, Tjitske, de Vries, Bert B. A., Ruiterkamp-Versteeg, Martina, Leijsten, Nico, Kwint, Michael, Derks, Ronny, Swinkels, Hilde, den Ouden, Amber, Pfundt, Rolph, Rinne, Tuula, de Leeuw, Nicole, Stegmann, Alexander P., Stevens, Servi J., van den Wijngaard, Arthur, Brunner, Han G., Yntema, Helger G., Gilissen, Christian, Nelen, Marcel R., and Vissers, Lisenka E. L. M.
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- 2023
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15. Clustering of Cardiac Transcriptome Profiles Reveals Unique: Subgroups of Dilated Cardiomyopathy Patients
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Verdonschot, Job A.J., Wang, Ping, Derks, Kasper W.J., Adriaens, Michiel E., Stroeks, Sophie L.V.M., Henkens, Michiel T.H.M., Raafs, Anne G., Sikking, Maurits, de Koning, Bart, van den Wijngaard, Arthur, Krapels, Ingrid P.C., Nabben, Miranda, Brunner, Han G., and Heymans, Stephane R.B.
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- 2023
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16. Neandertal Introgression Sheds Light on Modern Human Endocranial Globularity
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Gunz, Philipp, Tilot, Amanda K, Wittfeld, Katharina, Teumer, Alexander, Shapland, Chin Yang, van Erp, Theo GM, Dannemann, Michael, Vernot, Benjamin, Neubauer, Simon, Guadalupe, Tulio, Fernández, Guillén, Brunner, Han G, Enard, Wolfgang, Fallon, James, Hosten, Norbert, Völker, Uwe, Profico, Antonio, Di Vincenzo, Fabio, Manzi, Giorgio, Kelso, Janet, St. Pourcain, Beate, Hublin, Jean-Jacques, Franke, Barbara, Pääbo, Svante, Macciardi, Fabio, Grabe, Hans J, and Fisher, Simon E
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Genetics ,Neurosciences ,1.1 Normal biological development and functioning ,Underpinning research ,Neurological ,Generic health relevance ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Animals ,Biological Evolution ,Female ,Fossils ,Humans ,Hybridization ,Genetic ,Male ,Middle Aged ,Neanderthals ,Netherlands ,Phenotype ,Skull ,Young Adult ,Neandertal ,basal ganglia ,brain shape ,cerebellum ,evolution ,gene expression ,genetic association ,homo sapiens ,magnetic resonance imaging ,myelination ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Developmental Biology - Abstract
One of the features that distinguishes modern humans from our extinct relatives and ancestors is a globular shape of the braincase [1-4]. As the endocranium closely mirrors the outer shape of the brain, these differences might reflect altered neural architecture [4, 5]. However, in the absence of fossil brain tissue, the underlying neuroanatomical changes as well as their genetic bases remain elusive. To better understand the biological foundations of modern human endocranial shape, we turn to our closest extinct relatives: the Neandertals. Interbreeding between modern humans and Neandertals has resulted in introgressed fragments of Neandertal DNA in the genomes of present-day non-Africans [6, 7]. Based on shape analyses of fossil skull endocasts, we derive a measure of endocranial globularity from structural MRI scans of thousands of modern humans and study the effects of introgressed fragments of Neandertal DNA on this phenotype. We find that Neandertal alleles on chromosomes 1 and 18 are associated with reduced endocranial globularity. These alleles influence expression of two nearby genes, UBR4 and PHLPP1, which are involved in neurogenesis and myelination, respectively. Our findings show how integration of fossil skull data with archaic genomics and neuroimaging can suggest developmental mechanisms that may contribute to the unique modern human endocranial shape.
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- 2019
17. Clinical Risk Score to Predict Pathogenic Genotypes in Patients With Dilated Cardiomyopathy
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Escobar-Lopez, Luis, Ochoa, Juan Pablo, Royuela, Ana, Verdonschot, Job A.J., Dal Ferro, Matteo, Espinosa, Maria Angeles, Sabater-Molina, Maria, Gallego-Delgado, Maria, Larrañaga-Moreira, Jose M., Garcia-Pinilla, Jose M., Basurte-Elorz, Maria Teresa, Rodríguez-Palomares, José F., Climent, Vicente, Bermudez-Jimenez, Francisco J., Mogollón-Jiménez, María Victoria, Lopez, Javier, Peña-Peña, Maria Luisa, Garcia-Alvarez, Ana, López-Abel, Bernardo, Ripoll-Vera, Tomas, Palomino-Doza, Julian, Bayes-Genis, Antoni, Brugada, Ramon, Idiazabal, Uxua, Mirelis, Jesus G., Dominguez, Fernando, Henkens, Michiel T.H.M., Krapels, Ingrid P.C., Brunner, Han G., Paldino, Alessia, Zaffalon, Denise, Mestroni, Luisa, Sinagra, Gianfranco, Heymans, Stephane R.B., Merlo, Marco, and Garcia-Pavia, Pablo
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- 2022
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18. Lessons learned from unsolicited findings in clinical exome sequencing of 16,482 individuals
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van der Schoot, Vyne, Haer-Wigman, Lonneke, Feenstra, Ilse, Tammer, Femke, Oerlemans, Anke J. M., van Koolwijk, Martine P. A., van Agt, Frans, Arens, Yvonne H. J. M., Brunner, Han G., Vissers, Lisenka E. L. M., and Yntema, Helger G.
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- 2022
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19. DTYMK is essential for genome integrity and neuronal survival
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Vanoevelen, Jo M., Bierau, Jörgen, Grashorn, Janine C., Lambrichs, Ellen, Kamsteeg, Erik-Jan, Bok, Levinus A., Wevers, Ron A., van der Knaap, Marjo S., Bugiani, Marianna, Frisk, Junmei Hu, Colnaghi, Rita, O’Driscoll, Mark, Hellebrekers, Debby M. E. I., Rodenburg, Richard, Ferreira, Carlos R., Brunner, Han G., van den Wijngaard, Arthur, Abdel-Salam, Ghada M. H., Wang, Liya, and Stumpel, Constance T. R. M.
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- 2022
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20. De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder
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Reijnders, Margot RF, Miller, Kerry A, Alvi, Mohsan, Goos, Jacqueline AC, Lees, Melissa M, de Burca, Anna, Henderson, Alex, Kraus, Alison, Mikat, Barbara, de Vries, Bert BA, Isidor, Bertrand, Kerr, Bronwyn, Marcelis, Carlo, Schluth-Bolard, Caroline, Deshpande, Charu, Ruivenkamp, Claudia AL, Wieczorek, Dagmar, Study, The Deciphering Developmental Disorders, Baralle, Diana, Blair, Edward M, Engels, Hartmut, Lüdecke, Hermann-Josef, Eason, Jacqueline, Santen, Gijs WE, Clayton-Smith, Jill, Chandler, Kate, Tatton-Brown, Katrina, Payne, Katelyn, Helbig, Katherine, Radtke, Kelly, Nugent, Kimberly M, Cremer, Kirsten, Strom, Tim M, Bird, Lynne M, Sinnema, Margje, Bitner-Glindzicz, Maria, van Dooren, Marieke F, Alders, Marielle, Koopmans, Marije, Brick, Lauren, Kozenko, Mariya, Harline, Megan L, Klaassens, Merel, Steinraths, Michelle, Cooper, Nicola S, Edery, Patrick, Yap, Patrick, Terhal, Paulien A, van der Spek, Peter J, Lakeman, Phillis, Taylor, Rachel L, Littlejohn, Rebecca O, Pfundt, Rolph, Mercimek-Andrews, Saadet, Stegmann, Alexander PA, Kant, Sarina G, McLean, Scott, Joss, Shelagh, Swagemakers, Sigrid MA, Douzgou, Sofia, Wall, Steven A, Küry, Sébastien, Calpena, Eduardo, Koelling, Nils, McGowan, Simon J, Twigg, Stephen RF, Mathijssen, Irene MJ, Nellaker, Christoffer, Brunner, Han G, and Wilkie, Andrew OM
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Biological Sciences ,Bioinformatics and Computational Biology ,Biomedical and Clinical Sciences ,Genetics ,Biotechnology ,Brain Disorders ,Human Genome ,Neurosciences ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Adolescent ,Adult ,Base Sequence ,Cell Line ,Child ,Child ,Preschool ,Facies ,Female ,Genetic Association Studies ,Humans ,Infant ,Inheritance Patterns ,Loss of Function Mutation ,Male ,Neurodevelopmental Disorders ,Protein Kinases ,RNA ,Messenger ,Translocation ,Genetic ,Young Adult ,Deciphering Developmental Disorders Study ,Tousled-like ,facial averaging ,haploinsufficiency ,intellectual disability ,kinase ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Next-generation sequencing is a powerful tool for the discovery of genes related to neurodevelopmental disorders (NDDs). Here, we report the identification of a distinct syndrome due to de novo or inherited heterozygous mutations in Tousled-like kinase 2 (TLK2) in 38 unrelated individuals and two affected mothers, using whole-exome and whole-genome sequencing technologies, matchmaker databases, and international collaborations. Affected individuals had a consistent phenotype, characterized by mild-borderline neurodevelopmental delay (86%), behavioral disorders (68%), severe gastro-intestinal problems (63%), and facial dysmorphism including blepharophimosis (82%), telecanthus (74%), prominent nasal bridge (68%), broad nasal tip (66%), thin vermilion of the upper lip (62%), and upslanting palpebral fissures (55%). Analysis of cell lines from three affected individuals showed that mutations act through a loss-of-function mechanism in at least two case subjects. Genotype-phenotype analysis and comparison of computationally modeled faces showed that phenotypes of these and other individuals with loss-of-function variants significantly overlapped with phenotypes of individuals with other variant types (missense and C-terminal truncating). This suggests that haploinsufficiency of TLK2 is the most likely underlying disease mechanism, leading to a consistent neurodevelopmental phenotype. This work illustrates the power of international data sharing, by the identification of 40 individuals from 26 different centers in 7 different countries, allowing the identification, clinical delineation, and genotype-phenotype evaluation of a distinct NDD caused by mutations in TLK2.
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- 2018
21. Reanalysis of exome negative patients with rare disease: a pragmatic workflow for diagnostic applications
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Schobers, Gaby, Schieving, Jolanda H., Yntema, Helger G., Pennings, Maartje, Pfundt, Rolph, Derks, Ronny, Hofste, Tom, de Wijs, Ilse, Wieskamp, Nienke, van den Heuvel, Simone, Galbany, Jordi Corominas, Gilissen, Christian, Nelen, Marcel, Brunner, Han G., Kleefstra, Tjitske, Kamsteeg, Erik-Jan, Willemsen, Michèl A. A. P., and Vissers, Lisenka E. L. M.
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- 2022
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22. Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes
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Staf strategisch beleid, Genetica Klinische Genetica, Child Health, Rots, Dmitrijs, Choufani, Sanaa, Faundes, Victor, Dingemans, Alexander J.M., Joss, Shelagh, Foulds, Nicola, Jones, Elizabeth A., Stewart, Sarah, Vasudevan, Pradeep, Dabir, Tabib, Park, Soo Mi, Jewell, Rosalyn, Brown, Natasha, Pais, Lynn, Jacquemont, Sébastien, Jizi, Khadijé, Ravenswaaij-Arts, Conny M.A.van, Kroes, Hester Y., Stumpel, Constance T.R.M., Ockeloen, Charlotte W., Diets, Illja J., Nizon, Mathilde, Vincent, Marie, Cogné, Benjamin, Besnard, Thomas, Kambouris, Marios, Anderson, Emily, Zackai, Elaine H., McDougall, Carey, Donoghue, Sarah, O'Donnell-Luria, Anne, Valivullah, Zaheer, O'Leary, Melanie, Srivastava, Siddharth, Byers, Heather, Leslie, Nancy, Mazzola, Sarah, Tiller, George E., Vera, Moin, Shen, Joseph J., Boles, Richard, Jain, Vani, Brischoux-Boucher, Elise, Kinning, Esther, Simpson, Brittany N., Giltay, Jacques C., Harris, Jacqueline, Keren, Boris, Guimier, Anne, Marijon, Pierre, de Vries, Bert B.A., Motter, Constance S., Mendelsohn, Bryce A., Coffino, Samantha, Gerkes, Erica H., Afenjar, Alexandra, Visconti, Paola, Bacchelli, Elena, Maestrini, Elena, Delahaye-Duriez, Andree, Gooch, Catherine, Hendriks, Yvonne, Adams, Hieab, Thauvin-Robinet, Christel, Josephi-Taylor, Sarah, Bertoli, Marta, Parker, Michael J., Rutten, Julie W., Caluseriu, Oana, Vernon, Hilary J., Kaziyev, Jonah, Zhu, Jia, Kremen, Jessica, Frazier, Zoe, Osika, Hailey, Breault, David, Nair, Sreelata, Lewis, Suzanne M.E., Ceroni, Fabiola, Viggiano, Marta, Posar, Annio, Brittain, Helen, Giovanna, Traficante, Giulia, Gori, Quteineh, Lina, Ha-Vinh Leuchter, Russia, Zonneveld-Huijssoon, Evelien, Mellado, Cecilia, Marey, Isabelle, Coudert, Alicia, Aracena Alvarez, Mariana Inés, Kennis, Milou G.P., Bouman, Arianne, Roifman, Maian, Amorós Rodríguez, María Inmaculada, Ortigoza-Escobar, Juan Dario, Vernimmen, Vivian, Sinnema, Margje, Pfundt, Rolph, Brunner, Han G., Vissers, Lisenka E.L.M., Kleefstra, Tjitske, Weksberg, Rosanna, Banka, Siddharth, Staf strategisch beleid, Genetica Klinische Genetica, Child Health, Rots, Dmitrijs, Choufani, Sanaa, Faundes, Victor, Dingemans, Alexander J.M., Joss, Shelagh, Foulds, Nicola, Jones, Elizabeth A., Stewart, Sarah, Vasudevan, Pradeep, Dabir, Tabib, Park, Soo Mi, Jewell, Rosalyn, Brown, Natasha, Pais, Lynn, Jacquemont, Sébastien, Jizi, Khadijé, Ravenswaaij-Arts, Conny M.A.van, Kroes, Hester Y., Stumpel, Constance T.R.M., Ockeloen, Charlotte W., Diets, Illja J., Nizon, Mathilde, Vincent, Marie, Cogné, Benjamin, Besnard, Thomas, Kambouris, Marios, Anderson, Emily, Zackai, Elaine H., McDougall, Carey, Donoghue, Sarah, O'Donnell-Luria, Anne, Valivullah, Zaheer, O'Leary, Melanie, Srivastava, Siddharth, Byers, Heather, Leslie, Nancy, Mazzola, Sarah, Tiller, George E., Vera, Moin, Shen, Joseph J., Boles, Richard, Jain, Vani, Brischoux-Boucher, Elise, Kinning, Esther, Simpson, Brittany N., Giltay, Jacques C., Harris, Jacqueline, Keren, Boris, Guimier, Anne, Marijon, Pierre, de Vries, Bert B.A., Motter, Constance S., Mendelsohn, Bryce A., Coffino, Samantha, Gerkes, Erica H., Afenjar, Alexandra, Visconti, Paola, Bacchelli, Elena, Maestrini, Elena, Delahaye-Duriez, Andree, Gooch, Catherine, Hendriks, Yvonne, Adams, Hieab, Thauvin-Robinet, Christel, Josephi-Taylor, Sarah, Bertoli, Marta, Parker, Michael J., Rutten, Julie W., Caluseriu, Oana, Vernon, Hilary J., Kaziyev, Jonah, Zhu, Jia, Kremen, Jessica, Frazier, Zoe, Osika, Hailey, Breault, David, Nair, Sreelata, Lewis, Suzanne M.E., Ceroni, Fabiola, Viggiano, Marta, Posar, Annio, Brittain, Helen, Giovanna, Traficante, Giulia, Gori, Quteineh, Lina, Ha-Vinh Leuchter, Russia, Zonneveld-Huijssoon, Evelien, Mellado, Cecilia, Marey, Isabelle, Coudert, Alicia, Aracena Alvarez, Mariana Inés, Kennis, Milou G.P., Bouman, Arianne, Roifman, Maian, Amorós Rodríguez, María Inmaculada, Ortigoza-Escobar, Juan Dario, Vernimmen, Vivian, Sinnema, Margje, Pfundt, Rolph, Brunner, Han G., Vissers, Lisenka E.L.M., Kleefstra, Tjitske, Weksberg, Rosanna, and Banka, Siddharth
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- 2024
23. Comprehensive EHMT1 variants analysis broadens genotype-phenotype associations and molecular mechanisms in Kleefstra syndrome
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Genetica, Genetica Klinische Genetica, Genetica Sectie Genoomdiagnostiek, Child Health, Rots, Dmitrijs, Bouman, Arianne, Yamada, Ayumi, Levy, Michael, Dingemans, Alexander J.M., de Vries, Bert B.A., Ruiterkamp-Versteeg, Martina, de Leeuw, Nicole, Ockeloen, Charlotte W., Pfundt, Rolph, de Boer, Elke, Kummeling, Joost, van Bon, Bregje, van Bokhoven, Hans, Kasri, Nael Nadif, Venselaar, Hanka, Alders, Marielle, Kerkhof, Jennifer, McConkey, Haley, Kuechler, Alma, Elffers, Bart, van Beeck Calkoen, Rixje, Hofman, Susanna, Smith, Audrey, Valenzuela, Maria Irene, Srivastava, Siddharth, Frazier, Zoe, Maystadt, Isabelle, Piscopo, Carmelo, Merla, Giuseppe, Balasubramanian, Meena, Santen, Gijs W.E., Metcalfe, Kay, Park, Soo Mi, Pasquier, Laurent, Banka, Siddharth, Donnai, Dian, Weisberg, Daniel, Strobl-Wildemann, Gertrud, Wagemans, Annemieke, Vreeburg, Maaike, Baralle, Diana, Foulds, Nicola, Scurr, Ingrid, Brunetti-Pierri, Nicola, van Hagen, Johanna M., Bijlsma, Emilia K., Hakonen, Anna H., Courage, Carolina, Genevieve, David, Pinson, Lucile, Forzano, Francesca, Deshpande, Charu, Kluskens, Maria L., Welling, Lindsey, Plomp, Astrid S., Vanhoutte, Els K., Kalsner, Louisa, Hol, Janna A., Putoux, Audrey, Lazier, Johanna, Vasudevan, Pradeep, Ames, Elizabeth, O'Shea, Jessica, Lederer, Damien, Fleischer, Julie, O'Connor, Mary, Pauly, Melissa, Vasileiou, Georgia, Reis, André, Kiraly-Borri, Catherine, Bouman, Arjan, Barnett, Chris, Nezarati, Marjan, Borch, Lauren, Beunders, Gea, Özcan, Kübra, Miot, Stéphanie, Volker-Touw, Catharina M.L., van Gassen, Koen L.I., Cappuccio, Gerarda, Janssens, Katrien, Mor, Nofar, Shomer, Inna, Dominissini, Dan, Tedder, Matthew L., Muir, Alison M., Sadikovic, Bekim, Brunner, Han G., Vissers, Lisenka E.L.M., Shinkai, Yoichi, Kleefstra, Tjitske, Genetica, Genetica Klinische Genetica, Genetica Sectie Genoomdiagnostiek, Child Health, Rots, Dmitrijs, Bouman, Arianne, Yamada, Ayumi, Levy, Michael, Dingemans, Alexander J.M., de Vries, Bert B.A., Ruiterkamp-Versteeg, Martina, de Leeuw, Nicole, Ockeloen, Charlotte W., Pfundt, Rolph, de Boer, Elke, Kummeling, Joost, van Bon, Bregje, van Bokhoven, Hans, Kasri, Nael Nadif, Venselaar, Hanka, Alders, Marielle, Kerkhof, Jennifer, McConkey, Haley, Kuechler, Alma, Elffers, Bart, van Beeck Calkoen, Rixje, Hofman, Susanna, Smith, Audrey, Valenzuela, Maria Irene, Srivastava, Siddharth, Frazier, Zoe, Maystadt, Isabelle, Piscopo, Carmelo, Merla, Giuseppe, Balasubramanian, Meena, Santen, Gijs W.E., Metcalfe, Kay, Park, Soo Mi, Pasquier, Laurent, Banka, Siddharth, Donnai, Dian, Weisberg, Daniel, Strobl-Wildemann, Gertrud, Wagemans, Annemieke, Vreeburg, Maaike, Baralle, Diana, Foulds, Nicola, Scurr, Ingrid, Brunetti-Pierri, Nicola, van Hagen, Johanna M., Bijlsma, Emilia K., Hakonen, Anna H., Courage, Carolina, Genevieve, David, Pinson, Lucile, Forzano, Francesca, Deshpande, Charu, Kluskens, Maria L., Welling, Lindsey, Plomp, Astrid S., Vanhoutte, Els K., Kalsner, Louisa, Hol, Janna A., Putoux, Audrey, Lazier, Johanna, Vasudevan, Pradeep, Ames, Elizabeth, O'Shea, Jessica, Lederer, Damien, Fleischer, Julie, O'Connor, Mary, Pauly, Melissa, Vasileiou, Georgia, Reis, André, Kiraly-Borri, Catherine, Bouman, Arjan, Barnett, Chris, Nezarati, Marjan, Borch, Lauren, Beunders, Gea, Özcan, Kübra, Miot, Stéphanie, Volker-Touw, Catharina M.L., van Gassen, Koen L.I., Cappuccio, Gerarda, Janssens, Katrien, Mor, Nofar, Shomer, Inna, Dominissini, Dan, Tedder, Matthew L., Muir, Alison M., Sadikovic, Bekim, Brunner, Han G., Vissers, Lisenka E.L.M., Shinkai, Yoichi, and Kleefstra, Tjitske
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- 2024
24. Refining the 9q34.3 microduplication syndrome reveals mild neurodevelopmental features associated with a distinct global DNA methylation profile
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Rots, Dmitrijs, Rooney, Kathleen, Relator, Raissa, Kerkhof, Jennifer, Mcconkey, Haley, Pfundt, Rolph, Marcelis, Carlo, Willemsen, Marjolein H., van Hagen, Johanna M., Zwijnenburg, Petra, Alders, Marielle, Ounap, Katrin, Reimand, Tiia, Fjodorova, Olga, Berland, Siren, Liahjell, Eva Benedicte, Bojovic, Ognjen, Kriek, Marjolein, Ruivenkamp, Claudia, Bonati, Maria Teresa, Brunner, Han G., Vissers, Lisenka E. L. M., Sadikovic, Bekim, Kleefstra, Tjitske, Rots, Dmitrijs, Rooney, Kathleen, Relator, Raissa, Kerkhof, Jennifer, Mcconkey, Haley, Pfundt, Rolph, Marcelis, Carlo, Willemsen, Marjolein H., van Hagen, Johanna M., Zwijnenburg, Petra, Alders, Marielle, Ounap, Katrin, Reimand, Tiia, Fjodorova, Olga, Berland, Siren, Liahjell, Eva Benedicte, Bojovic, Ognjen, Kriek, Marjolein, Ruivenkamp, Claudia, Bonati, Maria Teresa, Brunner, Han G., Vissers, Lisenka E. L. M., Sadikovic, Bekim, and Kleefstra, Tjitske
- Abstract
Precise regulation of gene expression is important for correct neurodevelopment. 9q34.3 deletions affecting the EHMT1 gene result in a syndromic neurodevelopmental disorder named Kleefstra syndrome. In contrast, duplications of the 9q34.3 locus encompassing EHMT1 have been suggested to cause developmental disorders, but only limited information has been available. We have identified 15 individuals from 10 unrelated families, with 9q34.3 duplications <1.5 Mb in size, encompassing EHMT1 entirely. Clinical features included mild developmental delay, mild intellectual disability or learning problems, autism spectrum disorder, and behavior problems. The individuals did not consistently display dysmorphic features, congenital anomalies, or growth abnormalities. DNA methylation analysis revealed a weak DNAm profile for the cases with 9q34.3 duplication encompassing EHMT1, which could segregate the majority of the affected cases from controls. This study shows that individuals with 9q34.3 duplications including EHMT1 gene present with mild non-syndromic neurodevelopmental disorders and DNA methylation changes different from Kleefstra syndrome.
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- 2024
25. Diagnostic exome-based preconception carrier testing in consanguineous couples: results from the first 100 couples in clinical practice
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Sallevelt, Suzanne C. E. H., Stegmann, Alexander P. A., de Koning, Bart, Velter, Crool, Steyls, Anja, van Esch, Melanie, Lakeman, Phillis, Yntema, Helger, Esteki, Masoud Zamani, de Die-Smulders, Christine E. M., Gilissen, Christian, van den Wijngaard, Arthur, Brunner, Han G., and Paulussen, Aimée D. C.
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- 2021
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26. The impact of unsolicited findings in clinical exome sequencing, a qualitative interview study
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Schoot, Vyne van der, Viellevoije, Simone J., Tammer, Femke, Brunner, Han G., Arens, Yvonne, Yntema, Helger G., and Oerlemans, Anke J. M.
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- 2021
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27. Long-read trio sequencing of individuals with unsolved intellectual disability
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Pauper, Marc, Kucuk, Erdi, Wenger, Aaron M., Chakraborty, Shreyasee, Baybayan, Primo, Kwint, Michael, van der Sanden, Bart, Nelen, Marcel R., Derks, Ronny, Brunner, Han G., Hoischen, Alexander, Vissers, Lisenka E. L. M., and Gilissen, Christian
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- 2021
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28. Metabolic Profiling Associates with Disease Severity in Nonischemic Dilated Cardiomyopathy
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Verdonschot, Job A.J., Wang, Ping, Van Bilsen, Marc, Hazebroek, Mark R., Merken, Jort J., Vanhoutte, Els K., Henkens, Michiel T.H.M., Van Den Wijngaard, Arthur, Glatz, Jan F.C., Krapels, Ingrid P.C., Brunner, Han G., Heymans, Stephane R.B., and Bierau, Jörgen
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- 2020
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29. Lessons learned from rapid exome sequencing for 575 critically ill patients across the broad spectrum of rare disease
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Marouane, Abderrahim, primary, Neveling, Kornelia, additional, Deden, A. Chantal, additional, van den Heuvel, Simone, additional, Zafeiropoulou, Dimitra, additional, Castelein, Steven, additional, van de Veerdonk, Frank, additional, Koolen, David A., additional, Simons, Annet, additional, Rodenburg, Richard, additional, Westra, Dineke, additional, Mensenkamp, Arjen R., additional, de Leeuw, Nicole, additional, Ligtenberg, Marjolijn, additional, Matthijsse, Rene, additional, Pfundt, Rolph, additional, Kamsteeg, Erik Jan, additional, Brunner, Han G., additional, Gilissen, Christian, additional, Feenstra, Ilse, additional, de Boode, Willem P., additional, Yntema, Helger G., additional, van Zelst-Stams, Wendy A. G., additional, Nelen, Marcel, additional, and Vissers, Lisenka E. L. M., additional
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- 2024
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30. Heterozygous variants that disturb the transcriptional repressor activity of FOXP4 cause a developmental disorder with speech/language delays and multiple congenital abnormalities
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Snijders Blok, Lot, Vino, Arianna, den Hoed, Joery, Underhill, Hunter R., Monteil, Danielle, Li, Hong, Reynoso Santos, Francis Jeshira, Chung, Wendy K., Amaral, Michelle D., Schnur, Rhonda E., Santiago-Sim, Teresa, Si, Yue, Brunner, Han G., Kleefstra, Tjitske, and Fisher, Simon E.
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- 2021
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31. De Novo Mutations in SON Disrupt RNA Splicing of Genes Essential for Brain Development and Metabolism, Causing an Intellectual-Disability Syndrome
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Kim, Jung-Hyun, Shinde, Deepali N, Reijnders, Margot RF, Hauser, Natalie S, Belmonte, Rebecca L, Wilson, Gregory R, Bosch, Daniëlle GM, Bubulya, Paula A, Shashi, Vandana, Petrovski, Slavé, Stone, Joshua K, Park, Eun Young, Veltman, Joris A, Sinnema, Margje, Stumpel, Connie TRM, Draaisma, Jos M, Nicolai, Joost, Genomics, University of Washington Center for Mendelian, Yntema, Helger G, Lindstrom, Kristin, de Vries, Bert BA, Jewett, Tamison, Santoro, Stephanie L, Vogt, Julie, Study, Deciphering Developmental Disorders, Bachman, Kristine K, Seeley, Andrea H, Krokosky, Alyson, Turner, Clesson, Rohena, Luis, Hempel, Maja, Kortüm, Fanny, Lessel, Davor, Neu, Axel, Strom, Tim M, Wieczorek, Dagmar, Bramswig, Nuria, Laccone, Franco A, Behunova, Jana, Rehder, Helga, Gordon, Christopher T, Rio, Marlène, Romana, Serge, Tang, Sha, El-Khechen, Dima, Cho, Megan T, McWalter, Kirsty, Douglas, Ganka, Baskin, Berivan, Begtrup, Amber, Funari, Tara, Schoch, Kelly, Stegmann, Alexander PA, Stevens, Servi JC, Zhang, Dong-Er, Traver, David, Yao, Xu, MacArthur, Daniel G, Brunner, Han G, Mancini, Grazia M, Myers, Richard M, Owen, Laurie B, Lim, Ssang-Taek, Stachura, David L, Vissers, Lisenka ELM, and Ahn, Eun-Young Erin
- Subjects
Brain Disorders ,Congenital Structural Anomalies ,Neurosciences ,Mental Health ,Clinical Research ,Genetics ,Pediatric ,Intellectual and Developmental Disabilities (IDD) ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Congenital ,Animals ,Brain ,DNA-Binding Proteins ,Developmental Disabilities ,Eye Abnormalities ,Female ,Genes ,Essential ,Haploinsufficiency ,Head ,Heterozygote ,Humans ,Intellectual Disability ,Male ,Metabolic Diseases ,Minor Histocompatibility Antigens ,Mutation ,Pedigree ,RNA Splicing ,RNA ,Messenger ,Spine ,Syndrome ,Zebrafish ,University of Washington Center for Mendelian Genomics ,Deciphering Developmental Disorders Study ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next-generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses conclusively confirming these variants, as well as the underlying molecular mechanisms explaining the diseases, are often lacking. Here, we report on an ID syndrome caused by de novo heterozygous loss-of-function (LoF) mutations in SON. The syndrome is characterized by ID and/or DD, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations. Knockdown of son in zebrafish resulted in severe malformation of the spine, brain, and eyes. Importantly, analyses of RNA from affected individuals revealed that genes critical for neuronal migration and cortex organization (TUBG1, FLNA, PNKP, WDR62, PSMD3, and HDAC6) and metabolism (PCK2, PFKL, IDH2, ACY1, and ADA) are significantly downregulated because of the accumulation of mis-spliced transcripts resulting from erroneous SON-mediated RNA splicing. Our data highlight SON as a master regulator governing neurodevelopment and demonstrate the importance of SON-mediated RNA splicing in human development.
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- 2016
32. The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant
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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
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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.
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- 2016
33. DVL3 Alleles Resulting in a −1 Frameshift of the Last Exon Mediate Autosomal-Dominant Robinow Syndrome
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White, Janson J, Mazzeu, Juliana F, Hoischen, Alexander, Bayram, Yavuz, Withers, Marjorie, Gezdirici, Alper, Kimonis, Virginia, Steehouwer, Marloes, Jhangiani, Shalini N, Muzny, Donna M, Gibbs, Richard A, Genomics, Baylor-Hopkins Center for Mendelian, van Bon, Bregje WM, Sutton, V Reid, Lupski, James R, Brunner, Han G, and Carvalho, Claudia MB
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Rare Diseases ,Congenital Structural Anomalies ,Clinical Research ,Pediatric ,2.1 Biological and endogenous factors ,Aetiology ,Congenital ,Adaptor Proteins ,Signal Transducing ,Alleles ,Base Sequence ,Codon ,Nonsense ,Craniofacial Abnormalities ,Dishevelled Proteins ,Dwarfism ,Exons ,Female ,Frameshift Mutation ,Genetic Variation ,Humans ,Limb Deformities ,Congenital ,Male ,Molecular Sequence Data ,Phosphoproteins ,Proto-Oncogene Proteins ,Receptor Tyrosine Kinase-like Orphan Receptors ,Sequence Analysis ,DNA ,Sequence Deletion ,Urogenital Abnormalities ,Wnt Proteins ,Wnt-5a Protein ,Baylor-Hopkins Center for Mendelian Genomics ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Robinow syndrome is a rare congenital disorder characterized by mesomelic limb shortening, genital hypoplasia, and distinctive facial features. Recent reports have identified, in individuals with dominant Robinow syndrome, a specific type of variant characterized by being uniformly located in the penultimate exon of DVL1 and resulting in a -1 frameshift allele with a premature termination codon that escapes nonsense-mediated decay. Here, we studied a cohort of individuals who had been clinically diagnosed with Robinow syndrome but who had not received a molecular diagnosis from variant studies of DVL1, WNT5A, and ROR2. Because of the uniform location of frameshift variants in DVL1-mediated Robinow syndrome and the functional redundancy of DVL1, DVL2, and DVL3, we elected to pursue direct Sanger sequencing of the penultimate exon of DVL1 and its paralogs DVL2 and DVL3 to search for potential disease-associated variants. Remarkably, targeted sequencing identified five unrelated individuals harboring heterozygous, de novo frameshift variants in DVL3, including two splice acceptor mutations and three 1 bp deletions. Similar to the variants observed in DVL1-mediated Robinow syndrome, all variants in DVL3 result in a -1 frameshift, indicating that these highly specific alterations might be a common cause of dominant Robinow syndrome. Here, we review the current knowledge of these peculiar variant alleles in DVL1- and DVL3-mediated Robinow syndrome and further elucidate the phenotypic features present in subjects with DVL1 and DVL3 frameshift mutations.
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- 2016
34. DVL3 Alleles Resulting in a -1 Frameshift of the Last Exon Mediate Autosomal-Dominant Robinow Syndrome.
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White, Janson J, Mazzeu, Juliana F, Hoischen, Alexander, Bayram, Yavuz, Withers, Marjorie, Gezdirici, Alper, Kimonis, Virginia, Steehouwer, Marloes, Jhangiani, Shalini N, Muzny, Donna M, Gibbs, Richard A, Baylor-Hopkins Center for Mendelian Genomics, van Bon, Bregje WM, Sutton, V Reid, Lupski, James R, Brunner, Han G, and Carvalho, Claudia MB
- Subjects
Baylor-Hopkins Center for Mendelian Genomics ,Humans ,Dwarfism ,Craniofacial Abnormalities ,Limb Deformities ,Congenital ,Urogenital Abnormalities ,Adaptor Proteins ,Signal Transducing ,Proto-Oncogene Proteins ,Phosphoproteins ,Codon ,Nonsense ,Sequence Analysis ,DNA ,Sequence Deletion ,Base Sequence ,Frameshift Mutation ,Alleles ,Exons ,Molecular Sequence Data ,Female ,Male ,Wnt Proteins ,Genetic Variation ,Receptor Tyrosine Kinase-like Orphan Receptors ,Wnt-5a Protein ,Dishevelled Proteins ,Rare Diseases ,Congenital Structural Anomalies ,Clinical Research ,Pediatric ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Congenital ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Robinow syndrome is a rare congenital disorder characterized by mesomelic limb shortening, genital hypoplasia, and distinctive facial features. Recent reports have identified, in individuals with dominant Robinow syndrome, a specific type of variant characterized by being uniformly located in the penultimate exon of DVL1 and resulting in a -1 frameshift allele with a premature termination codon that escapes nonsense-mediated decay. Here, we studied a cohort of individuals who had been clinically diagnosed with Robinow syndrome but who had not received a molecular diagnosis from variant studies of DVL1, WNT5A, and ROR2. Because of the uniform location of frameshift variants in DVL1-mediated Robinow syndrome and the functional redundancy of DVL1, DVL2, and DVL3, we elected to pursue direct Sanger sequencing of the penultimate exon of DVL1 and its paralogs DVL2 and DVL3 to search for potential disease-associated variants. Remarkably, targeted sequencing identified five unrelated individuals harboring heterozygous, de novo frameshift variants in DVL3, including two splice acceptor mutations and three 1 bp deletions. Similar to the variants observed in DVL1-mediated Robinow syndrome, all variants in DVL3 result in a -1 frameshift, indicating that these highly specific alterations might be a common cause of dominant Robinow syndrome. Here, we review the current knowledge of these peculiar variant alleles in DVL1- and DVL3-mediated Robinow syndrome and further elucidate the phenotypic features present in subjects with DVL1 and DVL3 frameshift mutations.
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- 2016
35. Spectrum of congenital anomalies among VACTERL cases: a EUROCAT population-based study
- Author
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van de Putte, Romy, van Rooij, Iris A. L. M., Marcelis, Carlo L. M., Guo, Michel, Brunner, Han G., Addor, Marie-Claude, Cavero-Carbonell, Clara, Dias, Carlos M., Draper, Elizabeth S., Etxebarriarteun, Larraitz, Gatt, Miriam, Haeusler, Martin, Khoshnood, Babak, Klungsoyr, Kari, Kurinczuk, Jenny J., Lanzoni, Monica, Latos-Bielenska, Anna, Luyt, Karen, O’Mahony, Mary T., Miller, Nicola, Mullaney, Carmel, Nelen, Vera, Neville, Amanda J., Perthus, Isabelle, Pierini, Anna, Randrianaivo, Hanitra, Rankin, Judith, Rissmann, Anke, Rouget, Florence, Schaub, Bruno, Tucker, David, Wellesley, Diana, Wiesel, Awi, Zymak-Zakutnia, Natalya, Loane, Maria, Barisic, Ingeborg, de Walle, Hermien E. K., Roeleveld, Nel, and Bergman, Jorieke E. H.
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- 2020
- Full Text
- View/download PDF
36. The Matchmaker Exchange: A Platform for Rare Disease Gene Discovery
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Philippakis, Anthony A, Azzariti, Danielle R, Beltran, Sergi, Brookes, Anthony J, Brownstein, Catherine A, Brudno, Michael, Brunner, Han G, Buske, Orion J, Carey, Knox, Doll, Cassie, Dumitriu, Sergiu, Dyke, Stephanie OM, den Dunnen, Johan T, Firth, Helen V, Gibbs, Richard A, Girdea, Marta, Gonzalez, Michael, Haendel, Melissa A, Hamosh, Ada, Holm, Ingrid A, Huang, Lijia, Hurles, Matthew E, Hutton, Ben, Krier, Joel B, Misyura, Andriy, Mungall, Christopher J, Paschall, Justin, Paten, Benedict, Robinson, Peter N, Schiettecatte, François, Sobreira, Nara L, Swaminathan, Ganesh J, Taschner, Peter E, Terry, Sharon F, Washington, Nicole L, Züchner, Stephan, Boycott, Kym M, and Rehm, Heidi L
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Biological Sciences ,Genetics ,Human Genome ,Database Management Systems ,Databases ,Genetic ,Genetic Association Studies ,Genetic Predisposition to Disease ,Humans ,Information Dissemination ,Rare Diseases ,Software ,matchmaking ,rare disease ,genomic API ,gene discovery ,Matchmaker Exchange ,GA4GH ,IRDiRC ,Clinical Sciences ,Genetics & Heredity ,Clinical sciences - Abstract
There are few better examples of the need for data sharing than in the rare disease community, where patients, physicians, and researchers must search for "the needle in a haystack" to uncover rare, novel causes of disease within the genome. Impeding the pace of discovery has been the existence of many small siloed datasets within individual research or clinical laboratory databases and/or disease-specific organizations, hoping for serendipitous occasions when two distant investigators happen to learn they have a rare phenotype in common and can "match" these cases to build evidence for causality. However, serendipity has never proven to be a reliable or scalable approach in science. As such, the Matchmaker Exchange (MME) was launched to provide a robust and systematic approach to rare disease gene discovery through the creation of a federated network connecting databases of genotypes and rare phenotypes using a common application programming interface (API). The core building blocks of the MME have been defined and assembled. Three MME services have now been connected through the API and are available for community use. Additional databases that support internal matching are anticipated to join the MME network as it continues to grow.
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- 2015
37. Variants in CUL4B are Associated with Cerebral Malformations
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Vulto-van Silfhout, Anneke T, Nakagawa, Tadashi, Bahi-Buisson, Nadia, Haas, Stefan A, Hu, Hao, Bienek, Melanie, Vissers, Lisenka ELM, Gilissen, Christian, Tzschach, Andreas, Busche, Andreas, Müsebeck, Jörg, Rump, Patrick, Mathijssen, Inge B, Avela, Kristiina, Somer, Mirja, Doagu, Fatma, Philips, Anju K, Rauch, Anita, Baumer, Alessandra, Voesenek, Krysta, Poirier, Karine, Vigneron, Jacqueline, Amram, Daniel, Odent, Sylvie, Nawara, Magdalena, Obersztyn, Ewa, Lenart, Jacek, Charzewska, Agnieszka, Lebrun, Nicolas, Fischer, Ute, Nillesen, Willy M, Yntema, Helger G, Järvelä, Irma, Ropers, Hans-Hilger, de Vries, Bert BA, Brunner, Han G, van Bokhoven, Hans, Raymond, F Lucy, Willemsen, Michèl AAP, Chelly, Jamel, Xiong, Yue, Barkovich, A James, Kalscheuer, Vera M, Kleefstra, Tjitske, and de Brouwer, Arjan PM
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Clinical Research ,Intellectual and Developmental Disabilities (IDD) ,Brain Disorders ,Neurosciences ,Pediatric ,Rare Diseases ,Congenital Structural Anomalies ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Adolescent ,Adult ,Brain ,Cell Cycle Proteins ,Cells ,Cultured ,Child ,Child ,Preschool ,Cullin Proteins ,Genetic Association Studies ,HEK293 Cells ,Humans ,Infant ,Male ,Malformations of Cortical Development ,Mental Retardation ,X-Linked ,Middle Aged ,Nerve Tissue Proteins ,Pedigree ,Sequence Analysis ,DNA ,Young Adult ,CUL4B ,WDR62 ,cortical dysplasia ,hydrocephalus ,intellectual disability ,mutation ,Clinical Sciences ,Genetics & Heredity ,Clinical sciences - Abstract
Variants in cullin 4B (CUL4B) are a known cause of syndromic X-linked intellectual disability. Here, we describe an additional 25 patients from 11 families with variants in CUL4B. We identified nine different novel variants in these families and confirmed the pathogenicity of all nontruncating variants. Neuroimaging data, available for 15 patients, showed the presence of cerebral malformations in ten patients. The cerebral anomalies comprised malformations of cortical development (MCD), ventriculomegaly, and diminished white matter volume. The phenotypic heterogeneity of the cerebral malformations might result from the involvement of CUL-4B in various cellular pathways essential for normal brain development. Accordingly, we show that CUL-4B interacts with WDR62, a protein in which variants were previously identified in patients with microcephaly and a wide range of MCD. This interaction might contribute to the development of cerebral malformations in patients with variants in CUL4B.
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- 2015
38. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data
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Thompson, Paul M, Stein, Jason L, Medland, Sarah E, Hibar, Derrek P, Vasquez, Alejandro Arias, Renteria, Miguel E, Toro, Roberto, Jahanshad, Neda, Schumann, Gunter, Franke, Barbara, Wright, Margaret J, Martin, Nicholas G, Agartz, Ingrid, Alda, Martin, Alhusaini, Saud, Almasy, Laura, Almeida, Jorge, Alpert, Kathryn, Andreasen, Nancy C, Andreassen, Ole A, Apostolova, Liana G, Appel, Katja, Armstrong, Nicola J, Aribisala, Benjamin, Bastin, Mark E, Bauer, Michael, Bearden, Carrie E, Bergmann, Ørjan, Binder, Elisabeth B, Blangero, John, Bockholt, Henry J, Bøen, Erlend, Bois, Catherine, Boomsma, Dorret I, Booth, Tom, Bowman, Ian J, Bralten, Janita, Brouwer, Rachel M, Brunner, Han G, Brohawn, David G, Buckner, Randy L, Buitelaar, Jan, Bulayeva, Kazima, Bustillo, Juan R, Calhoun, Vince D, Cannon, Dara M, Cantor, Rita M, Carless, Melanie A, Caseras, Xavier, Cavalleri, Gianpiero L, Chakravarty, M Mallar, Chang, Kiki D, Ching, Christopher RK, Christoforou, Andrea, Cichon, Sven, Clark, Vincent P, Conrod, Patricia, Coppola, Giovanni, Crespo-Facorro, Benedicto, Curran, Joanne E, Czisch, Michael, Deary, Ian J, de Geus, Eco JC, den Braber, Anouk, Delvecchio, Giuseppe, Depondt, Chantal, de Haan, Lieuwe, de Zubicaray, Greig I, Dima, Danai, Dimitrova, Rali, Djurovic, Srdjan, Dong, Hongwei, Donohoe, Gary, Duggirala, Ravindranath, Dyer, Thomas D, Ehrlich, Stefan, Ekman, Carl Johan, Elvsåshagen, Torbjørn, Emsell, Louise, Erk, Susanne, Espeseth, Thomas, Fagerness, Jesen, Fears, Scott, Fedko, Iryna, Fernández, Guillén, Fisher, Simon E, Foroud, Tatiana, Fox, Peter T, Francks, Clyde, Frangou, Sophia, Frey, Eva Maria, Frodl, Thomas, Frouin, Vincent, Garavan, Hugh, Giddaluru, Sudheer, Glahn, David C, Godlewska, Beata, Goldstein, Rita Z, Gollub, Randy L, and Grabe, Hans J
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Biological Psychology ,Health Sciences ,Psychology ,Mental Illness ,Biomedical Imaging ,Human Genome ,Genetics ,Brain Disorders ,Mental Health ,Neurosciences ,Schizophrenia ,2.1 Biological and endogenous factors ,Mental health ,Neurological ,Good Health and Well Being ,Brain Mapping ,Cooperative Behavior ,Genome-Wide Association Study ,Humans ,Meta-Analysis as Topic ,Neuroimaging ,MRI ,GWAS ,Consortium ,Meta-analysis ,Multi-site ,Alzheimer’s Disease Neuroimaging Initiative ,EPIGEN Consortium ,IMAGEN Consortium ,Saguenay Youth Study (SYS) Group ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Experimental Psychology ,Biomedical and clinical sciences ,Health sciences - Abstract
The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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- 2014
39. Loss-of-function HDAC8 mutations cause a phenotypic spectrum of Cornelia de Lange syndrome-like features, ocular hypertelorism, large fontanelle and X-linked inheritance.
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Kaiser, Frank J, Ansari, Morad, Braunholz, Diana, Concepción Gil-Rodríguez, María, Decroos, Christophe, Wilde, Jonathan J, Fincher, Christopher T, Kaur, Maninder, Bando, Masashige, Amor, David J, Atwal, Paldeep S, Bahlo, Melanie, Bowman, Christine M, Bradley, Jacquelyn J, Brunner, Han G, Clark, Dinah, Del Campo, Miguel, Di Donato, Nataliya, Diakumis, Peter, Dubbs, Holly, Dyment, David A, Eckhold, Juliane, Ernst, Sarah, Ferreira, Jose C, Francey, Lauren J, Gehlken, Ulrike, Guillén-Navarro, Encarna, Gyftodimou, Yolanda, Hall, Bryan D, Hennekam, Raoul, Hudgins, Louanne, Hullings, Melanie, Hunter, Jennifer M, Yntema, Helger, Innes, A Micheil, Kline, Antonie D, Krumina, Zita, Lee, Hane, Leppig, Kathleen, Lynch, Sally Ann, Mallozzi, Mark B, Mannini, Linda, McKee, Shane, Mehta, Sarju G, Micule, Ieva, Care4Rare Canada Consortium, Mohammed, Shehla, Moran, Ellen, Mortier, Geert R, Moser, Joe-Ann S, Noon, Sarah E, Nozaki, Naohito, Nunes, Luis, Pappas, John G, Penney, Lynette S, Pérez-Aytés, Antonio, Petersen, Michael B, Puisac, Beatriz, Revencu, Nicole, Roeder, Elizabeth, Saitta, Sulagna, Scheuerle, Angela E, Schindeler, Karen L, Siu, Victoria M, Stark, Zornitza, Strom, Samuel P, Thiese, Heidi, Vater, Inga, Willems, Patrick, Williamson, Kathleen, Wilson, Louise C, University of Washington Center for Mendelian Genomics, Hakonarson, Hakon, Quintero-Rivera, Fabiola, Wierzba, Jolanta, Musio, Antonio, Gillessen-Kaesbach, Gabriele, Ramos, Feliciano J, Jackson, Laird G, Shirahige, Katsuhiko, Pié, Juan, Christianson, David W, Krantz, Ian D, Fitzpatrick, David R, and Deardorff, Matthew A
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Care4Rare Canada Consortium ,University of Washington Center for Mendelian Genomics ,Humans ,Hypertelorism ,De Lange Syndrome ,Eye Abnormalities ,Histone Deacetylases ,Repressor Proteins ,Cohort Studies ,Sequence Alignment ,Amino Acid Sequence ,Phenotype ,Mutation ,Missense ,Molecular Sequence Data ,Child ,Child ,Preschool ,Infant ,Female ,Male ,Genes ,X-Linked ,Cranial Fontanelles ,Genetics ,Rare Diseases ,Dental/Oral and Craniofacial Disease ,Intellectual and Developmental Disabilities (IDD) ,Pediatric ,Brain Disorders ,2.1 Biological and endogenous factors ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,Aetiology ,Congenital ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder with distinct facies, growth failure, intellectual disability, distal limb anomalies, gastrointestinal and neurological disease. Mutations in NIPBL, encoding a cohesin regulatory protein, account for >80% of cases with typical facies. Mutations in the core cohesin complex proteins, encoded by the SMC1A, SMC3 and RAD21 genes, together account for ∼5% of subjects, often with atypical CdLS features. Recently, we identified mutations in the X-linked gene HDAC8 as the cause of a small number of CdLS cases. Here, we report a cohort of 38 individuals with an emerging spectrum of features caused by HDAC8 mutations. For several individuals, the diagnosis of CdLS was not considered prior to genomic testing. Most mutations identified are missense and de novo. Many cases are heterozygous females, each with marked skewing of X-inactivation in peripheral blood DNA. We also identified eight hemizygous males who are more severely affected. The craniofacial appearance caused by HDAC8 mutations overlaps that of typical CdLS but often displays delayed anterior fontanelle closure, ocular hypertelorism, hooding of the eyelids, a broader nose and dental anomalies, which may be useful discriminating features. HDAC8 encodes the lysine deacetylase for the cohesin subunit SMC3 and analysis of the functional consequences of the missense mutations indicates that all cause a loss of enzymatic function. These data demonstrate that loss-of-function mutations in HDAC8 cause a range of overlapping human developmental phenotypes, including a phenotypically distinct subgroup of CdLS.
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- 2014
40. Clinical-grade whole genome sequencing-based haplarithmisis enables all forms of preimplantation genetic testing
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Janssen, Anouk E.J., primary, Koeck, Rebekka M., additional, Essers, Rick, additional, van Dijk, Wanwisa, additional, Drusedau, Marion, additional, Meekels, Jeroen, additional, Yaldiz, Burcu, additional, van de Vorst, Maartje, additional, Cao, Ping, additional, de Koning, Bart, additional, Hellebrekers, Debby M.E.I., additional, Stevens, Servi J.C., additional, Sun, Su Ming, additional, Heijligers, Malou, additional, de Munnik, Sonja A., additional, van Uum, Chris M.J., additional, Achten, Jelle, additional, Hamers, Lars, additional, Naghdi, Marjan, additional, Vissers, Lisenka E.L.M., additional, van Golde, Ron J.T., additional, de Wert, Guido, additional, Dreesen, Jos C.F.M., additional, de Die-Smulders, Christine, additional, Coonen, Edith, additional, Brunner, Han G., additional, van den Wijngaard, Arthur, additional, Paulussen, Aimee D.C., additional, and Zamani Esteki, Masoud, additional
- Published
- 2023
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41. Exploring uncertainties regarding unsolicited findings in genetic testing
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van der Schoot, Vyne, primary, van der Meer, Eline, additional, Hillen, Marij A., additional, Yntema, Helger G., additional, Brunner, Han G., additional, and Oerlemans, Anke J.M., additional
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- 2023
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42. Cardiac Inflammation Impedes Response to Cardiac Resynchronization Therapy in Patients with Idiopathic Dilated Cardiomyopathy
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Verdonschot, Job A.J., Merken, Jort J., van Stipdonk, Antonius M.W., Pliger, Philipp, Derks, Kasper W.J., Wang, Ping, Henkens, Michiel T.H.M., van Paassen, Pieter, Abdul Hamid, Myrurgia A., van Empel, Vanessa P.M., Knackstedt, Christian, Luermans, Justin G.L.M., Crijns, Harry J.G.M., Rocca, Hans-Peter Brunner-La, Brunner, Han G., Poelzl, Gerhard, Vernooy, Kevin, Heymans, Stephane R.B., and Hazebroek, Mark R.
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- 2020
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43. Genome-wide association analysis of anti-TNF drug response in patients with rheumatoid arthritis
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Mirkov, Maša Umiċeviċ, Cui, Jing, Vermeulen, Sita H, Stahl, Eli A, Toonen, Erik JM, Makkinje, Remco R, Lee, Annette T, Huizinga, Tom WJ, Allaart, Renee, Barton, Anne, Mariette, Xavier, Miceli, Corinne Richard, Criswell, Lindsey A, Tak, Paul P, de Vries, Niek, Saevarsdottir, Saedis, Padyukov, Leonid, Bridges, S Louis, van Schaardenburg, Dirk-Jan, Jansen, Tim L, Dutmer, Ellen AJ, van de Laar, Mart AFJ, Barrera, Pilar, Radstake, Timothy RDJ, van Riel, Piet LCM, Scheffer, Hans, Franke, Barbara, Brunner, Han G, Plenge, Robert M, Gregersen, Peter K, Guchelaar, Henk-Jan, and Coenen, Marieke JH
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Arthritis ,Rheumatoid Arthritis ,Genetics ,Autoimmune Disease ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Adalimumab ,Antibodies ,Monoclonal ,Antibodies ,Monoclonal ,Humanized ,Antirheumatic Agents ,Arthritis ,Rheumatoid ,DNA Mutational Analysis ,Drug Resistance ,Etanercept ,Female ,Gene Expression Regulation ,Genetic Markers ,Genome-Wide Association Study ,Humans ,Immunoglobulin G ,Infliximab ,Male ,Polymorphism ,Single Nucleotide ,Receptors ,Tumor Necrosis Factor ,Registries ,Tumor Necrosis Factor-alpha ,Anti-TNF ,Gene Polymorphism ,Pharmacogenetics ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
BackgroundTreatment strategies blocking tumour necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA). However, a significant subset of patients does not respond for unknown reasons. Currently, there are no means of identifying these patients before treatment. This study was aimed at identifying genetic factors predicting anti-TNF treatment outcome in patients with RA using a genome-wide association approach.MethodsWe conducted a multistage, genome-wide association study with a primary analysis of 2 557 253 single-nucleotide polymorphisms (SNPs) in 882 patients with RA receiving anti-TNF therapy included through the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry and the database of Apotheekzorg. Linear regression analysis of changes in the Disease Activity Score in 28 joints after 14 weeks of treatment was performed using an additive model. Markers with p
- Published
- 2013
44. Genetic architecture of subcortical brain structures in 38,851 individuals
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Satizabal, Claudia L., Adams, Hieab H. H., Hibar, Derrek P., White, Charles C., Knol, Maria J., Stein, Jason L., Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady V., Smith, Albert V., Bis, Joshua C., Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J., Yang, Jingyun, Yanek, Lisa R., Lee, Tom V., Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D., Desrivières, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavinia, Rentería, Miguel E., Kim, Sungeun, Hoehn, David, Armstrong, Nicola J., Chen, Qiang, Holmes, Avram J., den Braber, Anouk, Kloszewska, Iwona, Andersson, Micael, Espeseth, Thomas, Grimm, Oliver, Abramovic, Lucija, Alhusaini, Saud, Milaneschi, Yuri, Papmeyer, Martina, Axelsson, Tomas, Ehrlich, Stefan, Roiz-Santiañez, Roberto, Kraemer, Bernd, Håberg, Asta K., Jones, Hannah J., Pike, G. Bruce, Stein, Dan J., Stevens, Allison, Bralten, Janita, Vernooij, Meike W., Harris, Tamara B., Filippi, Irina, Witte, A. Veronica, Guadalupe, Tulio, Wittfeld, Katharina, Mosley, Thomas H., Becker, James T., Doan, Nhat Trung, Hagenaars, Saskia P., Saba, Yasaman, Cuellar-Partida, Gabriel, Amin, Najaf, Hilal, Saima, Nho, Kwangsik, Mirza-Schreiber, Nazanin, Arfanakis, Konstantinos, Becker, Diane M., Ames, David, Goldman, Aaron L., Lee, Phil H., Boomsma, Dorret I., Lovestone, Simon, Giddaluru, Sudheer, Le Hellard, Stephanie, Mattheisen, Manuel, Bohlken, Marc M., Kasperaviciute, Dalia, Schmaal, Lianne, Lawrie, Stephen M., Agartz, Ingrid, Walton, Esther, Tordesillas-Gutierrez, Diana, Davies, Gareth E., Shin, Jean, Ipser, Jonathan C., Vinke, Louis N., Hoogman, Martine, Jia, Tianye, Burkhardt, Ralph, Klein, Marieke, Crivello, Fabrice, Janowitz, Deborah, Carmichael, Owen, Haukvik, Unn K., Aribisala, Benjamin S., Schmidt, Helena, Strike, Lachlan T., Cheng, Ching-Yu, Risacher, Shannon L., Pütz, Benno, Fleischman, Debra A., Assareh, Amelia A., Mattay, Venkata S., Buckner, Randy L., Mecocci, Patrizia, Dale, Anders M., Cichon, Sven, Boks, Marco P., Matarin, Mar, Penninx, Brenda W. J. H., Calhoun, Vince D., Chakravarty, M. Mallar, Marquand, Andre F., Macare, Christine, Kharabian Masouleh, Shahrzad, Oosterlaan, Jaap, Amouyel, Philippe, Hegenscheid, Katrin, Rotter, Jerome I., Schork, Andrew J., Liewald, David C. M., de Zubicaray, Greig I., Wong, Tien Yin, Shen, Li, Sämann, Philipp G., Brodaty, Henry, Roffman, Joshua L., de Geus, Eco J. C., Tsolaki, Magda, Erk, Susanne, van Eijk, Kristel R., Cavalleri, Gianpiero L., van der Wee, Nic J. A., McIntosh, Andrew M., Gollub, Randy L., Bulayeva, Kazima B., Bernard, Manon, Richards, Jennifer S., Himali, Jayandra J., Loeffler, Markus, Rommelse, Nanda, Hoffmann, Wolfgang, Westlye, Lars T., Valdés Hernández, Maria C., Hansell, Narelle K., van Erp, Theo G. M., Wolf, Christiane, Kwok, John B. J., Vellas, Bruno, Heinz, Andreas, Olde Loohuis, Loes M., Delanty, Norman, Ho, Beng-Choon, Ching, Christopher R. K., Shumskaya, Elena, Singh, Baljeet, Hofman, Albert, van der Meer, Dennis, Homuth, Georg, Psaty, Bruce M., Bastin, Mark E., Montgomery, Grant W., Foroud, Tatiana M., Reppermund, Simone, Hottenga, Jouke-Jan, Simmons, Andrew, Meyer-Lindenberg, Andreas, Cahn, Wiepke, Whelan, Christopher D., van Donkelaar, Marjolein M. J., Yang, Qiong, Hosten, Norbert, Green, Robert C, Thalamuthu, Anbupalam, Mohnke, Sebastian, Hulshoff Pol, Hilleke E., Lin, Honghuang, Jack, Jr, Clifford R., Schofield, Peter R., Mühleisen, Thomas W., Maillard, Pauline, Potkin, Steven G., Wen, Wei, Fletcher, Evan, Toga, Arthur W., Gruber, Oliver, Huentelman, Matthew, Davey Smith, George, Launer, Lenore J., Nyberg, Lars, Jönsson, Erik G., Crespo-Facorro, Benedicto, Koen, Nastassja, Greve, Douglas N., Uitterlinden, André G., Weinberger, Daniel R., Steen, Vidar M., Fedko, Iryna O., Groenewold, Nynke A., Niessen, Wiro J., Toro, Roberto, Tzourio, Christophe, Longstreth, Jr, William T., Ikram, M. Kamran, Smoller, Jordan W., van Tol, Marie-Jose, Sussmann, Jessika E., Paus, Tomas, Lemaître, Hervé, Schroeter, Matthias L., Mazoyer, Bernard, Andreassen, Ole A., Holsboer, Florian, Depondt, Chantal, Veltman, Dick J., Turner, Jessica A., Pausova, Zdenka, Schumann, Gunter, van Rooij, Daan, Djurovic, Srdjan, Deary, Ian J., McMahon, Katie L., Müller-Myhsok, Bertram, Brouwer, Rachel M., Soininen, Hilkka, Pandolfo, Massimo, Wassink, Thomas H., Cheung, Joshua W., Wolfers, Thomas, Martinot, Jean-Luc, Zwiers, Marcel P., Nauck, Matthias, Melle, Ingrid, Martin, Nicholas G., Kanai, Ryota, Westman, Eric, Kahn, René S., Sisodiya, Sanjay M., White, Tonya, Saremi, Arvin, van Bokhoven, Hans, Brunner, Han G., Völzke, Henry, Wright, Margaret J., van ‘t Ent, Dennis, Nöthen, Markus M., Ophoff, Roel A., Buitelaar, Jan K., Fernández, Guillén, Sachdev, Perminder S., Rietschel, Marcella, van Haren, Neeltje E. M., Fisher, Simon E., Beiser, Alexa S., Francks, Clyde, Saykin, Andrew J., Mather, Karen A., Romanczuk-Seiferth, Nina, Hartman, Catharina A., DeStefano, Anita L., Heslenfeld, Dirk J., Weiner, Michael W., Walter, Henrik, Hoekstra, Pieter J., Nyquist, Paul A., Franke, Barbara, Bennett, David A., Grabe, Hans J., Johnson, Andrew D., Chen, Christopher, van Duijn, Cornelia M., Lopez, Oscar L., Fornage, Myriam, Wardlaw, Joanna M., Schmidt, Reinhold, DeCarli, Charles, De Jager, Philip L., Villringer, Arno, Debette, Stéphanie, Gudnason, Vilmundur, Medland, Sarah E., Shulman, Joshua M., Thompson, Paul M., Seshadri, Sudha, and Ikram, M. Arfan
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- 2019
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45. Next-generation phenotyping using computer vision algorithms in rare genomic neurodevelopmental disorders
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van der Donk, Roos, Jansen, Sandra, Schuurs-Hoeijmakers, Janneke H. M., Koolen, David A., Goltstein, Lia C. M. J., Hoischen, Alexander, Brunner, Han G., Kemmeren, Patrick, Nellåker, Christoffer, Vissers, Lisenka E. L. M., de Vries, Bert B. A., and Hehir-Kwa, Jayne Y.
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- 2019
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46. Assessment of fibroblast nuclear morphology aids interpretation of LMNA variants
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van Tienen, Florence H. J., Lindsey, Patrick J., Kamps, Miriam A. F., Krapels, Ingrid P., Ramaekers, Frans C. S., Brunner, Han G., van den Wijngaard, Arthur, and Broers, Jos L. V.
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- 2019
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47. 1 in 38 individuals at risk of a dominant medically actionable disease
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Haer-Wigman, Lonneke, van der Schoot, Vyne, Feenstra, Ilse, Vulto-van Silfhout, Anneke T., Gilissen, Christian, Brunner, Han G., Vissers, Lisenka E. L. M., and Yntema, Helger G.
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- 2019
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48. Genetic variants for head size share genes and pathways with cancer
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Amouyel, Philippe, Arfanakis, Konstantinos, Aribisala, Benjamin S., Bastin, Mark E., Chauhan, Ganesh, Chen, Christopher, Cheng, Ching-Yu, de Jager, Philip L., Deary, Ian J., Fleischman, Debra A., Gottesman, Rebecca F., Gudnason, Vilmundur, Hilal, Saima, Hofer, Edith, Janowitz, Deborah, Jukema, J. Wouter, Liewald, David C.M., Lopez, Lorna M., Lopez, Oscar, Luciano, Michelle, Martinez, Oliver, Niessen, Wiro J., Nyquist, Paul, Rotter, Jerome I., Rundek, Tatjana, Sacco, Ralph L., Schmidt, Helena, Tiemeier, Henning, Trompet, Stella, van der Grond, Jeroen, Völzke, Henry, Wardlaw, Joanna M., Yanek, Lisa, Yang, Jingyun, Agartz, Ingrid, Alhusaini, Saud, Almasy, Laura, Ames, David, Amunts, Katrin, Andreassen, Ole A., Armstrong, Nicola, Bernard, Manon, Blangero, John, Blanken, Laura M.E., Boks, Marco P., Boomsma, Dorret I., Brickman, Adam M., Brodaty, Henry, Buckner, Randy L., Buitelaar, Jan K., Cannon, Dara M., Carr, Vaughan J., Catts, Stanley V., Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R.K., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Davies, Gareth E., de Geus, Eco J.C., de Zubicaray, Greig I., den Braber, Anouk, Desrivières, Sylvane, Dillman, Allissa, Djurovic, Srdjan, Drevets, Wayne C., Duggirala, Ravi, Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernández, Guillén, Fisher, Simon E., Foroud, Tatiana M., Ge, Tian, Giddaluru, Sudheer, Glahn, David C., Goldman, Aaron L., Green, Robert C., Greven, Corina U., Grimm, Oliver, Hansell, Narelle K., Hartman, Catharina A., Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans, Hibar, Derrek P., Ho, Beng-Choon, Hoekstra, Pieter J., Holmes, Avram J., Hoogman, Martine, Hottenga, Jouke-Jan, Hulshoff Pol, Hilleke E., Jablensky, Assen, Jenkinson, Mark, Jia, Tianye, Jöckel, Karl-Heinz, Jönsson, Erik G., Kim, Sungeun, Klein, Marieke, Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Le Hellard, Stephanie, Lemaître, Hervé, Loughland, Carmel, Marquand, Andre F., Martin, Nicholas G., Martinot, Jean-Luc, Matarin, Mar, Mathalon, Daniel H., Mather, Karen A., Mattay, Venkata S., McDonald, Colm, McMahon, Francis J., McMahon, Katie L., E, Rebekah, McWhirter, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Michie, Patricia T., Milaneschi, Yuri, Morris, Derek W., Mowry, Bryan, Nho, Kwangsik, Nichols, Thomas E., Nöthen, Markus N., Olvera, Rene L., Oosterlaan, Jaap, Ophoff, Roel A., Pandolfo, Massimo, Pantelis, Christos, Pappa, Irene, Penninx, Brenda, Pike, G. Bruce, Rasser, Paul E., Rentería, Miguel E., Reppermund, Simone, Rietschel, Marcella, Risacher, Shannon L., Romanczuk-Seiferth, Nina, Rose, Emma Jane, Sachdev, Perminder S., Sämann, Philipp G., Saykin, Andrew J., Schall, Ulrich, Schofield, Peter R., Schramm, Sara, Schumann, Gunter, Scott, Rodney, Shen, Li, Sisodiya, Sanjay M., Soininen, Hilkka, Sprooten, Emma, Srikanth, Velandai, Steen, Vidar M., Strike, Lachlan T., Thalamuthu, Anbupalam, Toga, Arthur W., Tooney, Paul, Tordesillas-Gutiérrez, Diana, Turner, Jessica A., Valdés Hernández, Maria del C., van der Meer, Dennis, Van der Wee, Nic J.A., Van Haren, Neeltje E.M., van 't Ent, Dennis, Veltman, Dick J., Walter, Henrik, Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westlye, Lars T., Westman, Eric, Winkler, Anderson M., Woldehawariat, Girma, Wright, Margaret J., Wu, Jingqin, Knol, Maria J., Poot, Raymond A., Evans, Tavia E., Satizabal, Claudia L., Mishra, Aniket, Sargurupremraj, Muralidharan, van der Auwera, Sandra, Duperron, Marie-Gabrielle, Jian, Xueqiu, Hostettler, Isabel C., van Dam-Nolen, Dianne H.K., Lamballais, Sander, Pawlak, Mikolaj A., Lewis, Cora E., Carrion-Castillo, Amaia, van Erp, Theo G.M., Reinbold, Céline S., Shin, Jean, Scholz, Markus, Håberg, Asta K., Kämpe, Anders, Li, Gloria H.Y., Avinun, Reut, Atkins, Joshua R., Hsu, Fang-Chi, Amod, Alyssa R., Lam, Max, Tsuchida, Ami, Teunissen, Mariël W.A., Aygün, Nil, Patel, Yash, Liang, Dan, Beiser, Alexa S., Beyer, Frauke, Bis, Joshua C., Bos, Daniel, Bryan, R. Nick, Bülow, Robin, Caspers, Svenja, Catheline, Gwenaëlle, Cecil, Charlotte A.M., Dalvie, Shareefa, Dartigues, Jean-François, DeCarli, Charles, Enlund-Cerullo, Maria, Ford, Judith M., Franke, Barbara, Freedman, Barry I., Friedrich, Nele, Green, Melissa J., Haworth, Simon, Helmer, Catherine, Hoffmann, Per, Homuth, Georg, Ikram, M. Kamran, Jack, Clifford R., Jr., Jahanshad, Neda, Jockwitz, Christiane, Kamatani, Yoichiro, Knodt, Annchen R., Li, Shuo, Lim, Keane, Longstreth, W.T., Macciardi, Fabio, Mäkitie, Outi, Mazoyer, Bernard, Medland, Sarah E., Miyamoto, Susumu, Moebus, Susanne, Mosley, Thomas H., Muetzel, Ryan, Mühleisen, Thomas W., Nagata, Manabu, Nakahara, Soichiro, Palmer, Nicholette D., Pausova, Zdenka, Preda, Adrian, Quidé, Yann, Reay, William R., Roshchupkin, Gennady V., Schmidt, Reinhold, Schreiner, Pamela J., Setoh, Kazuya, Shapland, Chin Yang, Sidney, Stephen, St Pourcain, Beate, Stein, Jason L., Tabara, Yasuharu, Teumer, Alexander, Uhlmann, Anne, van der Lugt, Aad, Vernooij, Meike W., Werring, David J., Windham, B. Gwen, Witte, A. Veronica, Wittfeld, Katharina, Yang, Qiong, Yoshida, Kazumichi, Brunner, Han G., Le Grand, Quentin, Sim, Kang, Stein, Dan J., Bowden, Donald W., Cairns, Murray J., Hariri, Ahmad R., Cheung, Ching-Lung, Andersson, Sture, Villringer, Arno, Paus, Tomas, Cichon, Sven, Calhoun, Vince D., Crivello, Fabrice, Launer, Lenore J., White, Tonya, Koudstaal, Peter J., Houlden, Henry, Fornage, Myriam, Matsuda, Fumihiko, Grabe, Hans J., Ikram, M. Arfan, Debette, Stéphanie, Thompson, Paul M., Seshadri, Sudha, and Adams, Hieab H.H.
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- 2024
- Full Text
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49. Further delineation of the rare GDACCF (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies syndrome): genotype and phenotype of 22 patients withZNF148mutations
- Author
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Szakszon, Katalin, primary, Lourenco, Charles Marques, additional, Callewaert, Bert Louis, additional, Geneviève, David, additional, Rouxel, Flavien, additional, Morin, Denis, additional, Denommé-Pichon, Anne-Sophie, additional, Vitobello, Antonio, additional, Patterson, Wesley, additional, Louie, Raymond, additional, Pinto e Vairo, Filippo, additional, Klee, Eric, additional, Kaiwar, Charu, additional, Gavrilova, Ralitza H, additional, Agre, Katherine E, additional, Jacquemont, Sebastien, additional, Khadijé, Jizi, additional, Giltay, Jacques, additional, van Gassen, Koen, additional, Merő, Gabriella, additional, Gerkes, Erica, additional, Van Bon, Bregje W, additional, Rinne, Tuula, additional, Pfundt, Rolph, additional, Brunner, Han G, additional, Caluseriu, Oana, additional, Grasshoff, Ute, additional, Kehrer, Martin, additional, Haack, Tobias B, additional, Khelifa, Melik Malek, additional, Bergmann, Anke Katharina, additional, Cueto-González, Anna Maria, additional, Martorell, Ariadna Campos, additional, Ramachandrappa, Shwetha, additional, Sawyer, Lindsey B, additional, Fasel, Pascale, additional, Braun, Dominique, additional, Isis, Atallah, additional, Superti-Furga, Andrea, additional, McNiven, Vanda, additional, Chitayat, David, additional, Ahmed, Syed Anas, additional, Brennenstuhl, Heiko, additional, Schwaibolf, Eva MC, additional, Battisti, Gladys, additional, Parmentier, Benoit, additional, and Stevens, Servi J C, additional
- Published
- 2023
- Full Text
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50. Systemic Inflammation and Normocytic Anemia in DOCK11 Deficiency
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Block, Jana, primary, Rashkova, Christina, additional, Castanon, Irinka, additional, Zoghi, Samaneh, additional, Platon, Jessica, additional, Ardy, Rico C., additional, Fujiwara, Mitsuhiro, additional, Chaves, Beatriz, additional, Schoppmeyer, Rouven, additional, van der Made, Caspar I., additional, Jimenez Heredia, Raul, additional, Harms, Frederike L., additional, Alavi, Samin, additional, Alsina, Laia, additional, Sanchez Moreno, Paula, additional, Ávila Polo, Rainiero, additional, Cabrera-Pérez, Rocío, additional, Kostel Bal, Sevgi, additional, Pfajfer, Laurène, additional, Ransmayr, Bernhard, additional, Mautner, Anna-Katharina, additional, Kondo, Ryohei, additional, Tinnacher, Anna, additional, Caldera, Michael, additional, Schuster, Michael, additional, Domínguez Conde, Cecilia, additional, Platzer, René, additional, Salzer, Elisabeth, additional, Boyer, Thomas, additional, Brunner, Han G., additional, Nooitgedagt-Frons, Judith E., additional, Iglesias, Estíbaliz, additional, Deyà-Martinez, Angela, additional, Camacho-Lovillo, Marisol, additional, Menche, Jörg, additional, Bock, Christoph, additional, Huppa, Johannes B., additional, Pickl, Winfried F., additional, Distel, Martin, additional, Yoder, Jeffrey A., additional, Traver, David, additional, Engelhardt, Karin R., additional, Linden, Tobias, additional, Kager, Leo, additional, Hannich, J. Thomas, additional, Hoischen, Alexander, additional, Hambleton, Sophie, additional, Illsinger, Sabine, additional, Da Costa, Lydie, additional, Kutsche, Kerstin, additional, Chavoshzadeh, Zahra, additional, van Buul, Jaap D., additional, Antón, Jordi, additional, Calzada-Hernández, Joan, additional, Neth, Olaf, additional, Viaud, Julien, additional, Nishikimi, Akihiko, additional, Dupré, Loïc, additional, and Boztug, Kaan, additional
- Published
- 2023
- Full Text
- View/download PDF
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