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Genome sequencing identifies major causes of severe intellectual disability
Open accessAbstract
Severe intellectual disability (ID) occurs in 0.5% of newborns and is thought to be largely genetic in origin. The extensive genetic heterogeneity of this disorder requires a genome-wide detection of all types of genetic variation. Microarray studies and, more recently, exome sequencing have demonstrated the importance of de novo copy number variations (CNVs) and single-nucleotide variations (SNVs) in ID, but the majority of cases remain undiagnosed. Here we applied whole-genome sequencing to 50 patients with severe ID and their unaffected parents. All patients included had not received a molecular diagnosis after extensive genetic prescreening, including microarray-based CNV studies and exome sequencing. Notwithstanding this prescreening, 84 de novo SNVs affecting the coding region were identified, which showed a statistically significant enrichment of loss-of-function mutations as well as an enrichment for genes previously implicated in ID-related disorders. In addition, we identified eight de novo CNVs, including single-exon and intra-exonic deletions, as well as interchromosomal duplications. These CNVs affected known ID genes more frequently than expected. On the basis of diagnostic interpretation of all de novo variants, a conclusive genetic diagnosis was reached in 20 patients. Together with one compound heterozygous CNV causing disease in a recessive mode, this results in a diagnostic yield of 42% in this extensively studied cohort, and 62% as a cumulative estimate in an unselected cohort. These results suggest that de novo SNVs and CNVs affecting the coding region are a major cause of severe ID. Genome sequencing can be applied as a single genetic test to reliably identify and characterize the comprehensive spectrum of genetic variation, providing a genetic diagnosis in the majority of patients with severe ID.
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“Various genetic approaches have been successful in identifying the causes of more than 1,000 Mendelian, and fewer non-Mendelian, forms of neurodevelopmental disorders: prototypical examples are intellectual disability62–68, autism spectrum disorder (ASD)69–77, epilepsy78,79 and schizophrenia80–82.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [68]
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“Because of this bias, the phenotypic overlap between the groups is unclear; the prevalence of ASD in several of the ID/DD-ascertained cohorts is not quantified,13, 14, 15,18,19 and the prevalence of ID in the ASD-ascertained cohorts is known only for a minority subset of participants.11,12”
From Insufficient Evidence for “Autism-Specific” Genes (2020) · cites this paper as [18]
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“Additionally, whole-exome sequencing studies of other neurodevelopmental disorders have found enrichment for FMRP targets in rare mutations in schizophrenia81, intellectual disability68 and epilepsy78.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [68]
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Cites
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
O’Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., et al. (2012) · Nature · doi:10.1038/nature10989 · Cited by 2,165
Rate of de novo mutations and the importance of father’s age to disease risk
Kong, A., Frigge, M. L., Masson, G., Besenbacher, S., Sulem, P., Magnusson, G., Gudjonsson, S. A., Sigurdsson, A., Jonasdottir, A., Jonasdottir, A., et al. (2012) · Nature · doi:10.1038/nature11396 · Cited by 2,134
De novo mutations revealed by whole-exome sequencing are strongly associated with autism
Sanders, S. J., Murtha, M. T., Gupta, A. R., Murdoch, J. D., Raubeson, M. J., Willsey, A. J., Ercan-Sencicek, A. G., DiLullo, N. M., Parikshak, N. N., Stein, J. L., et al. (2012) · Nature · doi:10.1038/nature10945 · Cited by 2,084
Patterns and rates of exonic de novo mutations in autism spectrum disorders
Neale, B. M., Kou, Y., Liu, L., Ma’ayan, A., Samocha, K. E., Sabo, A., Lin, C.-F., Stevens, C., Wang, L.-S., Makarov, V., et al. (2012) · Nature · doi:10.1038/nature11011 · Cited by 1,734
Diagnostic exome sequencing in persons with severe intellectual disability
de Ligt, J., Willemsen, M. H., van Bon, B. W. M., Kleefstra, T., Yntema, H. G., Kroes, T., Vulto-van Silfhout, A. T., Koolen, D. A., de Vries, P., Gilissen, C., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1206524 · Cited by 1,546
Self-citationDe novo mutations in epileptic encephalopathies
Epi4K Consortium, & Epilepsy Phenome/Genome Project (2013) · Nature · doi:10.1038/nature12439 · Cited by 1,514
De Novo Gene Disruptions in Children on the Autistic Spectrum
Iossifov, I., Ronemus, M., Levy, D., Wang, Z., Hakker, I., Rosenbaum, J., Yamrom, B., Lee, Y.-H., Narzisi, G., Leotta, A., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.04.009 · Cited by 1,446
A Systematic Survey of Loss-of-Function Variants in Human Protein-Coding Genes
MacArthur, D. G., Balasubramanian, S., Frankish, A., Huang, N., Morris, J., Walter, K., Jostins, L., Habegger, L., Pickrell, J. K., Montgomery, S. B., et al. (2012) · Science · doi:10.1126/science.1215040 · Cited by 1,272
Human Genome Sequencing Using Unchained Base Reads on Self-Assembling DNA Nanoarrays
Drmanac, R., Sparks, A. B., Callow, M. J., Halpern, A. L., Burns, N. L., Kermani, B. G., Carnevali, P., Nazarenko, I., Nilsen, G. B., Yeung, G., et al. (2010) · Science · doi:10.1126/science.1181498 · Cited by 1,212
Research works printed but not linked: 1
- Bell, J. B. D., Sistermans, E. & Ramsden, S. C. Practice guidelines for the Interpretation and Reporting of Unclassified Variants (UVs) in Clinical Molecular Genetics (The UK Clinical Molecular Genetics Society and the Dutch Society of Clinical Genetic Laboratory Specialists, 2007)
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Study, D. D. D. (2017) · Nature · doi:10.1038/nature21062 · Cited by 1,480
Ashley, E. A. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.86 · Cited by 1,116
InterVar: Clinical Interpretation of Genetic Variants by the 2015 ACMG-AMP Guidelines
Li, Q., & Wang, K. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.01.004 · Cited by 1,057
Inferring the molecular and phenotypic impact of amino acid variants with MutPred2
Pejaver, V., Urresti, J., Lugo-Martinez, J., Pagel, K. A., Lin, G. N., Nam, H.-J., Mort, M., Cooper, D. N., Sebat, J., Iakoucheva, L. M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19669-x · Cited by 923
Advancing the understanding of autism disease mechanisms through genetics
de la Torre-Ubieta, L., Won, H., Stein, J. L., & Geschwind, D. H. (2016) · Nature Medicine · doi:10.1038/nm.4071 · Cited by 827
Genetic studies in intellectual disability and related disorders
Vissers, L. E. L. M., Gilissen, C., & Veltman, J. A. (2016) · Nature Reviews Genetics · doi:10.1038/nrg3999 · Cited by 761
Self-citationStructural variation in the 3D genome
Spielmann, M., Lupiáñez, D. G., & Mundlos, S. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0007-0 · Cited by 752
100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care — Preliminary Report
The 100, 0. G. P. P. I. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2035790 · Cited by 716
Psychiatric Genomics: An Update and an Agenda
Sullivan, P. F., Agrawal, A., Bulik, C. M., Andreassen, O. A., Børglum, A. D., Breen, G., Cichon, S., Edenberg, H. J., Faraone, S. V., Gelernter, J., et al. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.17030283 · Cited by 676
Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants
Belkadi, A., Bolze, A., Itan, Y., Cobat, A., Vincent, Q. B., Antipenko, A., Shang, L., Boisson, B., Casanova, J., & Abel, L. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1418631112 · Cited by 638
Neurodevelopmental Disorders: From Genetics to Functional Pathways
Parenti, I., Rabaneda, L. G., Schoen, H., & Novarino, G. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.05.004 · Cited by 687
Genetics and Genomics of Congenital Heart Disease
Zaidi, S., & Brueckner, M. K. (2017) · Circulation Research · doi:10.1161/circresaha.116.309140 · Cited by 612
Genetic Causes and Modifiers of Autism Spectrum Disorder
Rylaarsdam, L. E., & Guemez‐Gamboa, A. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00385 · Cited by 618
Lionel, A. C., Costain, G., Monfared, N., Walker, S., Reuter, M. S., Hosseini, S. M., Thiruvahindrapuram, B., Merico, D., Jobling, R., Nalpathamkalam, T., et al. (2018) · Genetics in Medicine · doi:10.1038/gim.2017.119 · Cited by 557
Soden, S. E., Saunders, C., Willig, L. K., Farrow, E., Smith, L. D., Petrikin, J. E., LePichon, J.-B., Miller, N., Thiffault, I., Dinwiddie, D. L., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3010076 · Cited by 525
Whole-genome sequencing of quartet families with autism spectrum disorder
Yuen, R. K. C., Thiruvahindrapuram, B., Merico, D., Walker, S., Tammimies, K., Hoang, N., Chrysler, C., Nalpathamkalam, T., Pellecchia, G., Liu, Y., et al. (2015) · Nature Medicine · doi:10.1038/nm.3792 · Cited by 514
Safran, M., Rosen, N., Twik, M., Barshir, R., Stein, T. I., Dahary, D., Fishilevich, S., & Lancet, D. (2021) · Springer eBooks · doi:10.1007/978-981-16-5812-9_2 · Cited by 492
Predicting the clinical impact of human mutation with deep neural networks
Sundaram, L., Gao, H., Padigepati, S. R., McRae, J. F., Li, Y., Kosmicki, J. A., Fritzilas, N., Hakenberg, J., Dutta, A., Shon, J. C., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0167-z · Cited by 505
Carss, K., Arno, G., Erwood, M., Stephens, J. C., Sanchis‐Juan, A., Hull, S., Mégy, K., Grozeva, D., Dewhurst, E. F., Malka, S., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.12.003 · Cited by 467
New insights into the generation and role of de novo mutations in health and disease
Acuña‐Hidalgo, R., Veltman, J. A., & Hoischen, A. (2016) · Genome biology · doi:10.1186/s13059-016-1110-1 · Cited by 474
Self-citationDeep intronic mutations and human disease
Vaz‐Drago, R., Custódio, N., & Carmo‐Fonseca, M. (2017) · Human Genetics · doi:10.1007/s00439-017-1809-4 · Cited by 477
High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies
Hamdan, F. F., Myers, C. T., Cossette, P., Lemay, P., Spiegelman, D., Laporte, A. D., Nassif, C., Diallo, O., Monlong, J., Cadieux-Dion, M., et al. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.09.008 · Cited by 445
Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia
Genovese, G., Fromer, M., Stahl, E. A., Ruderfer, D. M., Chambert, K., Landén, M., Moran, J. L., Purcell, S. M., Sklar, P., Sullivan, P. F., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4402 · Cited by 444
Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability
Lelieveld, S. H., Reijnders, M. R. F., Pfundt, R., Yntema, H. G., Kamsteeg, E.-J., de Vries, P., de Vries, B. B. A., Willemsen, M. H., Kleefstra, T., Löhner, K., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4352 · Cited by 442
Self-citationBreaking TADs: How Alterations of Chromatin Domains Result in Disease
Lupiáñez, D. G., Spielmann, M., & Mundlos, S. (2016) · Trends in Genetics · doi:10.1016/j.tig.2016.01.003 · Cited by 439
Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders
Parikshak, N. N., Gandal, M. J., & Geschwind, D. H. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3934 · Cited by 430
Long-Read Sequencing Emerging in Medical Genetics
Mantere, T., Kersten, S., & Hoischen, A. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00426 · Cited by 462
Self-citationErratum: Guidelines for diagnostic next-generation sequencing
Matthijs, G., Souche, E. L., Alders, M. M., Corveleyn, A., Eck, S. H., Feenstra, I., Race, V., Sistermans, E. A., Sturm, M., Weiss, M. M., et al. (2016) · European Journal of Human Genetics · doi:10.1038/ejhg.2016.63 · Cited by 431
Self-citationDe Novo Mutations in Moderate or Severe Intellectual Disability
Hamdan, F. F., Srour, M., Capo-Chichi, J.-M., Daoud, H., Nassif, C., Patry, L., Massicotte, C., Ambalavanan, A., Spiegelman, D., Diallo, O., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004772 · Cited by 419
Tammimies, K., Marshall, C. R., Walker, S., Kaur, G., Thiruvahindrapuram, B., Lionel, A. C., Yuen, R. K. C., Uddin, M., Roberts, W., Weksberg, R., et al. (2015) · JAMA · doi:10.1001/jama.2015.10078 · Cited by 419
Rare variant discovery by deep whole-genome sequencing of 1,070 Japanese individuals
Nagasaki, M., Yasuda, J., Katsuoka, F., Nariai, N., Kojima, K., Kawai, Y., Yamaguchi‐Kabata, Y., Yokozawa, J., Danjoh, I., Saito, S., et al. (2015) · Nature Communications · doi:10.1038/ncomms9018 · Cited by 393
Mapping and phasing of structural variation in patient genomes using nanopore sequencing
Cretu-Stancu, M., van Roosmalen, M. J., Renkens, I., Nieboer, M. M., Middelkamp, S., de Ligt, J., Pregno, G., Giachino, D. F., Mandrile, G., Valle-Inclán, J. E., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01343-4 · Cited by 403
Sawyer, S. L., Hartley, T., Dyment, D. A., Beaulieu, C. L., Schwartzentruber, J., Smith, A. C., Bedford, H. M., Bernard, G., Bernier, F. P., Brais, B., et al. (2015) · Clinical Genetics · doi:10.1111/cge.12654 · Cited by 384
Factors influencing success of clinical genome sequencing across a broad spectrum of disorders
Taylor, J. C., Martin, H. C., Lise, S., Broxholme, J., Cazier, J., Rimmer, A., Kanapin, A. A., Lunter, G. A., Fiddy, S., Allan, C., et al. (2015) · Nature Genetics · doi:10.1038/ng.3304 · Cited by 377
From cohorts to molecules: adverse impacts of endocrine disrupting mixtures
Caporale, N., Leemans, M., Birgersson, L., Germain, P.-L., Cheroni, C., Borbély, G., Engdahl, E., Lindh, C., Bressan, R. B., Cavallo, F., et al. (2022) · Science · doi:10.1126/science.abe8244 · Cited by 368
Stavropoulos, D. J., Merico, D., Jobling, R. K., Bowdin, S. C., Monfared, N., Thiruvahindrapuram, B., Nalpathamkalam, T., Pellecchia, G., Yuen, R. K. C., Szego, M. J., et al. (2016) · npj Genomic Medicine · doi:10.1038/npjgenmed.2015.12 · Cited by 366
Self-citationClinical exome sequencing: results from 2819 samples reflecting 1000 families
Trujillano, D., Bertoli‐Avella, A. M., Kandaswamy, K. K., Weiss, M. E. R., Köster, J., Marais, A., Paknia, O., Schröder, R., García-Aznar, J. M., Werber, M., et al. (2016) · European Journal of Human Genetics · doi:10.1038/ejhg.2016.146 · Cited by 361
Clinical sequencing: is WGS the better WES?
Meienberg, J., Bruggmann, R., Oexle, K., & Mátyás, G. (2016) · Human Genetics · doi:10.1007/s00439-015-1631-9 · Cited by 358
Xue, Y., Ankala, A., Wilcox, W. R., & Hegde, M. (2014) · Genetics in Medicine · doi:10.1038/gim.2014.122 · Cited by 359
Genetic, environmental, and epigenetic factors involved in CAKUT
Nicolaou, N., Renkema, K. Y., Bongers, E. M. H. F., Giles, R. H., & Knoers, N. V. A. M. (2015) · Nature Reviews Nephrology · doi:10.1038/nrneph.2015.140 · Cited by 344
Computational pan-genomics: status, promises and challenges
Marschall, T., Marz, M., Abeel, T., Dijkstra, L., Dutilh, B. E., Ghaffaari, A., Kersey, P., Kloosterman, W. P., Mäkinen, V., Novak, A. M., et al. (2016) · Briefings in Bioinformatics · doi:10.1093/bib/bbw089 · Cited by 369
Parent-of-origin-specific signatures of de novo mutations
Goldmann, J. M., Wong, W. S. W., Pinelli, M., Farrah, T., Bodian, D. L., Stittrich, A., Glusman, G., Vissers, L. E. L. M., Hoischen, A., Roach, J. C., et al. (2016) · Nature Genetics · doi:10.1038/ng.3597 · Cited by 340
Self-citationTan, T. Y., Dillon, O. J., Stark, Z., SCHOFIELD, D. J., Alam, K., Shrestha, R. N., Chong, B., Phelan, D., Brett, G. R., Creed, E., et al. (2017) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2017.1755 · Cited by 327
A synaptic perspective of fragile X syndrome and autism spectrum Disorders.
Bagni, C., & Zukin, R. S. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.041 · Cited by 326
Kochinke, K., Zweier, C., Nijhof, B., Fencková, M., Čížek, P., Honti, F., Keerthikumar, S., Oortveld, M. A. W., Kleefstra, T., Kramer, J. M., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.11.024 · Cited by 337
Self-citationPottier, C., Bieniek, K. F., Finch, N., van de Vorst, M., Baker, M., Perkersen, R., Brown, P., Ravenscroft, T., van Blitterswijk, M., Nicholson, A. M., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1436-x · Cited by 312
Self-citationKaraca, E., Harel, T., Pehli̇van, D., Jhangiani, S. N., Gambin, T., Coban‐Akdemir, Z., Gonzaga-Jauregui, C. G., Erdin, S., Bayram, Y., Campbell, I. M., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.09.048 · Cited by 309
Blok, L. S., Madsen, E. C., Juusola, J., Gilissen, C., Baralle, D., Reijnders, M. R. F., Venselaar, H., Helsmoortel, C., Cho, M. T., Hoischen, A., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.07.004 · Cited by 301
Self-citationThe GABAA Receptor as a Therapeutic Target for Neurodevelopmental Disorders
Braat, S., & Kooy, R. F. (2015) · Neuron · doi:10.1016/j.neuron.2015.03.042 · Cited by 294
Smedley, D., Schubach, M., Jacobsen, J. O. B., Köhler, S., Zemojtel, T., Spielmann, M., Jäger, M., Hochheiser, H., Washington, N. L., McMurry, J. A., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.07.005 · Cited by 283
Synaptopathology Involved in Autism Spectrum Disorder
Guang, S., Pang, N., Deng, X., Yang, L., He, F. P., Wu, L., Chen, C., Yin, F., & Peng, J. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00470 · Cited by 298
Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders
Stray‐Pedersen, A., Sorte, H. S., Samarakoon, P. S., Gambin, T., Chinn, I. K., Coban‐Akdemir, Z., Erichsen, H. C., Forbes, L. R., Gu, S., Yuan, B., et al. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.05.042 · Cited by 281
The genetics of bipolar disorder
Gordovez, F. J. A., & McMahon, F. J. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0634-7 · Cited by 284
VarElect: the phenotype-based variation prioritizer of the GeneCards Suite
Stelzer, G., Plaschkes, I., Oz-Levi, D., Alkelai, A., Olender, T., Zimmerman, S., Twik, M., Belinky, F., Fishilevich, S., Nudel, R., et al. (2016) · BMC Genomics · doi:10.1186/s12864-016-2722-2 · Cited by 264
Turner, T. N., Hormozdiari, F., Duyzend, M., McClymont, S. A., Hook, P. W., Iossifov, I. H., Raja, A. N., Baker, C. A., Hoekzema, K., Stessman, H. A. F., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.11.023 · Cited by 272
Redin, C. E., Gérard, B., Lauer, J., Herenger, Y., Muller, J., Quartier, A., Masurel, A., Willems, M., Lesca, G., Chehadeh, S. E., et al. (2014) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2014-102554 · Cited by 274
Wiel, L., Baakman, C. A. B., Gilissen, D., Veltman, J. A., Vriend, G., & Gilissen, C. (2019) · Human Mutation · doi:10.1002/humu.23798 · Cited by 268
Self-citationRecommendations for clinical interpretation of variants found in non-coding regions of the genome
Ellingford, J. M., Ahn, J. W., Bagnall, R. D., Baralle, D., Barton, S., Campbell, C., Downes, K., Ellard, S., Duff‐Farrier, C. R. A., FitzPatrick, D. R., et al. (2022) · Genome Medicine · doi:10.1186/s13073-022-01073-3 · Cited by 274
Optical genome mapping enables constitutional chromosomal aberration detection
Mantere, T., Neveling, K., Pebrel‐Richard, C., Benoist, M., van de Zande, G., Kater‐Baats, E., Baatout, I., van Beek, R., Yammine, T., Oorsprong, M., et al. (2021) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2021.05.012 · Cited by 256
Self-citationHuman Structural Variation: Mechanisms of Chromosome Rearrangements
Weckselblatt, B., & Rudd, M. K. (2015) · Trends in Genetics · doi:10.1016/j.tig.2015.05.010 · Cited by 261
Post-zygotic Point Mutations Are an Underrecognized Source of De Novo Genomic Variation
Acuña‐Hidalgo, R., Bo, T., Kwint, M. P., van de Vorst, M., Pinelli, M., Veltman, J. A., Hoischen, A., Vissers, L. E. L. M., & Gilissen, C. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.05.008 · Cited by 246
Self-citationAnazi, S., Maddirevula, S., Faqeih, E., Alsedairy, H., Alzahrani, F., Shamseldin, H. E., Patel, N., Hashem, M., Ibrahim, N., Abdulwahab, F., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.113 · Cited by 242
Reuter, M. S., Tawamie, H., Buchert, R., Hosny Gebril, O., Froukh, T., Thiel, C., Uebe, S., Ekici, A. B., Krumbiegel, M., Zweier, C., et al. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2016.3798 · Cited by 241
Somatic mosaicism and neurodevelopmental disease
D’Gama, A. M., & Walsh, C. A. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0257-3 · Cited by 249
Whole exome sequencing of suspected mitochondrial patients in clinical practice
Wortmann, S. B., Koolen, D. A., Smeitink, J. A., den van Heuvel, L., & Rodenburg, R. J. (2015) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-015-9823-y · Cited by 233
Lessons learned from additional research analyses of unsolved clinical exome cases
Eldomery, M. K., Coban-Akdemir, Z., Harel, T., Rosenfeld, J. A., Gambin, T., Stray-Pedersen, A., Küry, S., Mercier, S., Lessel, D., Denecke, J., et al. (2017) · Genome Medicine · doi:10.1186/s13073-017-0412-6 · Cited by 230
Genetic Testing in Neurodevelopmental Disorders
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The road to precision psychiatry: translating genetics into disease mechanisms
Gandal, M. J., Leppa, V., Won, H., Parikshak, N. N., & Geschwind, D. H. (2016) · Nature Neuroscience · doi:10.1038/nn.4409 · Cited by 223
Tatton‐Brown, K., Loveday, C., Yost, S. E., Clarke, M., Ramsay, E., Zachariou, A., Elliott, A., Wylie, H., Ardissone, A., Rittinger, O., et al. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.03.010 · Cited by 229
Next-generation sequencing in Charcot–Marie–Tooth disease: opportunities and challenges
Pipis, M., Rossor, A. M., Laurá, M., & Reilly, M. M. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0254-5 · Cited by 225
Lelieveld, S. H., Spielmann, M., Mundlos, S., Veltman, J. A., & Gilissen, C. (2015) · Human Mutation · doi:10.1002/humu.22813 · Cited by 217
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Leppä, V., Kravitz, S. N., Martin, C. L., Andrieux, J., Caignec, C. L., Martin‐Coignard, D., DyBuncio, C. T., Sanders, S., Lowe, J. K., Cantor, R. M., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.06.036 · Cited by 229
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Hu, H., Kahrizi, K., Musante, L., Fattahi, Z., Herwig, R., Hosseini, M., Oppitz, C., Abedini, S. S., Suckow, V., Larti, F., et al. (2018) · Molecular Psychiatry · doi:10.1038/s41380-017-0012-2 · Cited by 225
Polymer physics predicts the effects of structural variants on chromatin architecture
Bianco, S., Lupiáñez, D. G., Chiariello, A. M., Annunziatella, C., Kraft, K., Schöpflin, R., Wittler, L., Andrey, G., Vingron, M., Pombo, A., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0098-8 · Cited by 215
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Lata, S., Marasà, M., Li, Y., Fasel, D. A., Groopman, E., Jobanputra, V., Rasouly, H. M., Mitrotti, A., Westland, R., Verbitsky, M., et al. (2018) · Annals of Internal Medicine · doi:10.7326/m17-1319 · Cited by 209
Collins, R. L., Brand, H., Redin, C. E., Hanscom, C., Antolik, C. W., Stone, M. R., Glessner, J., Mason, T., Pregno, G., Dorrani, N., et al. (2017) · Genome biology · doi:10.1186/s13059-017-1158-6 · Cited by 208
Aref-Eshghi, E., Bend, E. G., Colaiacovo, S., Caudle, M., Chakrabarti, R., Napier, M., Brick, L., Brady, L., Carere, D. A., Levy, M. A., et al. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2019.03.008 · Cited by 201
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Martin, H. C., Jones, W. D., McIntyre, R., Sanchez-Andrade, G., Sanderson, M., Stephenson, J. D., Jones, C. P., Handsaker, J., Gallone, G., Bruntraeger, M., et al. (2018) · Science · doi:10.1126/science.aar6731 · Cited by 201
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Posey, J. E., O’Donnell‐Luria, A., Chong, J. X., Harel, T., Jhangiani, S. N., Coban‐Akdemir, Z., Buyske, S. G., Pehli̇van, D., Carvalho, C. M. B., Baxter, S. M., et al. (2019) · Genetics in Medicine · doi:10.1038/s41436-018-0408-7 · Cited by 202
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Ewans, L., SCHOFIELD, D. J., Shrestha, R. N., Zhu, Y., Gayevskiy, V., Ying, K., Walsh, C., Lee, E., Kirk, E. P., Colley, A., et al. (2018) · Genetics in Medicine · doi:10.1038/gim.2018.39 · Cited by 196
Yavarna, T., Al-Dewik, N. I. E., Al‐Mureikhi, M., Ali, R., Al‐Mesaifri, F., Mahmoud, L., Shahbeck, N., Lakhani, S., AlMulla, M., Nawaz, Z., et al. (2015) · Human Genetics · doi:10.1007/s00439-015-1575-0 · Cited by 202
Pizzo, L., Jensen, M., Polyak, A., Rosenfeld, J. A., Mannik, K., Krishnan, A., McCready, E., Pichon, O., Le Caignec, C., Van Dijck, A., et al. (2019) · Genetics in Medicine · doi:10.1038/s41436-018-0266-3 · Cited by 193
Sangermano, R., Garanto, A., Khan, M., Runhart, E. H., Bauwens, M., Bax, N. M., van den Born, L. I., Khan, M. I., Cornelis, S. S., Verheij, J. B. G. M., et al. (2019) · Genetics in Medicine · doi:10.1038/s41436-018-0414-9 · Cited by 188
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Rodenburg, R. J. (2016) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2016.02.012 · Cited by 187
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Grozeva, D., Carss, K., Spasić-Bošković, O., Tejada, M., Gécz, J., Shaw, M. A., Corbett, M. A., Haan, E., Thompson, E. M., Friend, K. L., et al. (2015) · Human Mutation · doi:10.1002/humu.22901 · Cited by 192
Pfundt, R., del Rosario, M., Vissers, L. E. L. M., Kwint, M. P., Janssen, I. M., de Leeuw, N., Yntema, H. G., Nelen, M. R., Lugtenberg, D., Kamsteeg, E., et al. (2016) · Genetics in Medicine · doi:10.1038/gim.2016.163 · Cited by 180
Self-citationHarripaul, R., Vasli, N., Mikhailov, A., Rafiq, M. A., Mittal, K., Windpassinger, C., Sheikh, T. I., Noor, A., Mahmood, H., Downey, S., et al. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.60 · Cited by 175
Alfares, A. A., Aloraini, T., Alsubaie, L., AlIssa, A., Qudsi, A. A., Alahmad, A., Mutairi, F. A., Alswaid, A. F., Alothaim, A., Eyaid, W., et al. (2018) · Genetics in Medicine · doi:10.1038/gim.2018.41 · Cited by 173
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Sheikh, B. N., & Akhtar, A. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0072-4 · Cited by 178
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Myers, S. M., Challman, T. D., Bernier, R., Bourgeron, T., Chung, W. K., Constantino, J. N., Eichler, E. E., Jacquemont, S., Miller, D. T., Mitchell, K. J., et al. (2020) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2020.04.004 · Cited by 165
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van Karnebeek, C. D. M., Bonafé, L., Wen, X.-Y., Tarailo-Graovac, M., Balzano, S., Royer-Bertrand, B., Ashikov, A., Garavelli, L., Mammi, I., Turolla, L., et al. (2016) · Nature Genetics · doi:10.1038/ng.3578 · Cited by 164
Best practices for the interpretation and reporting of clinical whole genome sequencing
Austin-Tse, C. A., Jobanputra, V., Perry, D., Bick, D. P., Taft, R. J., Venner, E., Gibbs, R. A., Young, E. J., Barnett, S., Belmont, J. W., et al. (2022) · npj Genomic Medicine · doi:10.1038/s41525-022-00295-z · Cited by 164
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Dias, C., Estruch, S. B., Graham, S. A., McRae, J. F., Sawiak, S. J., Hurst, J. A., Joss, S. K., Holder, S., Morton, J. E. V., Turner, C., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.05.030 · Cited by 168
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van Nimwegen, K. J. M., van Soest, R. A., Veltman, J. A., Nelen, M. R., van der Wilt, G. J., Vissers, L. E. L. M., & Grutters, J. P. C. (2016) · Clinical Chemistry · doi:10.1373/clinchem.2016.258632 · Cited by 161
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UK10K, Riazuddin, S. A., Hussain, M., Razzaq, A., Iqbal, Z., Shahzad, M., Polla, D. L., Song, Y., van Beusekom, E., Khan, A. A., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.109 · Cited by 164
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Jiang, X., & Karlsen, T. H. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.154 · Cited by 155
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Bosch, D. G. M., Boonstra, F. N., de Leeuw, N., Pfundt, R., Nillesen, W. M., de Ligt, J., Gilissen, C., Jhangiani, S. N., Lupski, J. R., Cremers, F. P. M., et al. (2015) · European Journal of Human Genetics · doi:10.1038/ejhg.2015.186 · Cited by 155
Self-citation
Metadata
- Authors
- Gilissen, C., Hehir-Kwa, J. Y., Thung, D. T., van de Vorst, M., van Bon, B. W. M., Willemsen, M. H., Kwint, M., Janssen, I. M., Hoischen, A., Schenck, A., Leach, R., Klein, R., Tearle, R., Bo, T., Pfundt, R., Yntema, H. G., de Vries, B. B. A., Kleefstra, T., Brunner, H. G., Vissers, L. E. L. M., & Veltman, J. A.
- Affiliations
- Radboud University Nijmegen (NL)
- Radboud University Medical Center (NL)
- Complete Genomics (United States) (US)
- Central South University (CN)
- Corresponding author
- Veltman, Joris A.
- ORCID
- Venue
- Nature
- Published
- 2014-06-04
- Volume
- 511
- Issue
- 7509
- Pages
- 344-347
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2045392412
- Cited by
- 1,125
- References
- 29
- Citations by year
- 2026: 30 · 2025: 45 · 2024: 50 · 2023: 74 · 2022: 93 · 2021: 87 · 2020: 102 · 2019: 115 · 2018: 122 · 2017: 129 · 2016: 137 · 2015: 110 · 2014: 28
- FWCI
- 88.22
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (acceptedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- severe intellectual disability, de novo copy number variation, loss-of-function mutations, whole genome sequencing, genetic diagnosis, diagnostic yield, recessive inheritance, undiagnosed genetic disorders
- MeSH terms
- Chromosomes, Human, Pair 4, Humans, Male, Intellectual Disability, Mutation, Cohort Studies, Genome, Human, Sequence Analysis, DNA, Gene Duplication, Polymorphism, Single Nucleotide, Guanine Nucleotide Exchange Factors, Chromosomes, Human, X, DNA Copy Number Variations
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