Cited by 419Genetics and Neurodevelopmental DisordersGenomics and Rare DiseasesGenomic variations and chromosomal abnormalities

The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.

De Novo Mutations in Moderate or Severe Intellectual Disability

Open access

Hamdan, Fadi F., Srour, Myriam, Capo-Chichi, Jose-Mario, Daoud, Hussein, Nassif, Christina, Patry, Lysanne, Massicotte, Christine, Ambalavanan, Amirthagowri, Spiegelman, Dan, Diallo, Ousmane, Henrion, Edouard, Dionne-Laporte, Alexandre, Fougerat, Anne, Pshezhetsky, Alexey V., Venkateswaran, Sunita, Rouleau, Guy A., Michaud, Jacques L.·2014·PLoS Genetics

DOI 10.1371/journal.pgen.1004772PMC PMC4214635

Open this paper in CoChat — free account Open PDF

Abstract

Genetics is believed to have an important role in intellectual disability (ID). Recent studies have emphasized the involvement of de novo mutations (DNMs) in ID but the extent to which they contribute to its pathogenesis and the identity of the corresponding genes remain largely unknown. Here, we report a screen for DNMs in subjects with moderate or severe ID. We sequenced the exomes of 41 probands and their parents, and confirmed 81 DNMs affecting the coding sequence or consensus splice sites (1.98 DNMs/proband). We observed a significant excess of de novo single nucleotide substitutions and loss-of-function mutations in these cases compared to control subjects, suggesting that at least a subset of these variations are pathogenic. A total of 12 likely pathogenic DNMs were identified in genes previously associated with ID (ARID1B, CHD2, FOXG1, GABRB3, GATAD2B, GRIN2B, MBD5, MED13L, SETBP1, TBR1, TCF4, WDR45), resulting in a diagnostic yield of ∼29%. We also identified 12 possibly pathogenic DNMs in genes (HNRNPU, WAC, RYR2, SET, EGR1, MYH10, EIF2C1, COL4A3BP, CHMP2A, PPP1CB, VPS4A, PPP2R2B) that have not previously been causally linked to ID. Interestingly, no case was explained by inherited mutations. Protein network analysis indicated that the products of many of these known and candidate genes interact with each other or with products of other ID-associated genes further supporting their involvement in ID. We conclude that DNMs represent a major cause of moderate or severe ID.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1371/journal.pgen.1004772

Cites

62 of 62 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Integrative genomics viewer
Robinson, J. T., Thorvaldsdóttir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G., & Mesirov, J. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1754 · Cited by 15,390
ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
Wang, K., Li, M., & Hakonarson, H. H. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq603 · Cited by 14,724
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 · cited 2×
“DNMs in TBR1 have been found in patients with ID and the variable presence of ASD or growth retardation [8,9,21,29,30].”
Background
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
De 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
Multiplex Targeted Sequencing Identifies Recurrently Mutated Genes in Autism Spectrum Disorders
O’Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., et al. (2012) · Science · doi:10.1126/science.1227764 · Cited by 1,240
Genome sequencing identifies major causes of severe intellectual disability
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., et al. (2014) · Nature · doi:10.1038/nature13394 · Cited by 1,125

Flagged first, then by citations

Show all 62 references

Sorted by citations

Gene expression elucidates functional impact of polygenic risk for schizophrenia
Fromer, M., Roussos, P., Sieberts, S. K., Johnson, J. S., Kavanagh, D. H., Perumal, T. M., Ruderfer, D. M., Oh, E. C., Topol, A., Shah, H. R., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4399 · Cited by 1,091
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
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
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000131 · Cited by 686
Methyl-cpG-binding domain proteins: readers of the epigenome
Du, Q., Luu, P.-L., Stirzaker, C., & Clark, S. J. (2015) · Epigenomics · doi:10.2217/epi.15.39 · Cited by 544
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
Autism genetics: opportunities and challenges for clinical translation
Vorstman, J. A. S., Parr, J. R., Moreno‐De‐Luca, D., Anney, R., Nürnberger, J. I., & Hallmayer, J. F. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.4 · Cited by 517
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
Self-citation
Ion Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies
Oyrer, J., Maljevic, S., Scheffer, I. E., Berkovic, S. F., Petrou, S., & Reid, C. A. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014456 · Cited by 315
The 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
De novo variants in neurodevelopmental disorders with epilepsy
Heyne, H., Singh, T., Stamberger, H., Jamra, R. A., Çağlayan, H., Craiu, D., Jonghe, P. D., Guerrini, R., Helbig, K. L., Koeleman, B. P. C., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0143-7 · Cited by 289
De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies
Myers, C. T., McMahon, J. M., Schneider, A. L., Petrovski, S., Allen, A. S., Carvill, G. L., Zemel, M., Saykally, J. E., LaCroix, A. J., Heinzen, E. L., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.06.003 · Cited by 287
Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications
Jiang, C.-C., Lin, L., Long, S., Ke, X., Fukunaga, K., Lu, Y., & Han, F. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01081-0 · Cited by 295
GRIN2B encephalopathy: novel findings on phenotype, variant clustering, functional consequences and treatment aspects
Platzer, K., Yuan, H., Schutz, H. M., Winschel, A., Chen, W., Hu, C., Kusumoto, H., Heyne, H., Helbig, K. L., Tang, S., et al. (2017) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2016-104509 · Cited by 262
Advancing epilepsy genetics in the genomic era
Myers, C. T., & Mefford, H. C. (2015) · Genome Medicine · doi:10.1186/s13073-015-0214-7 · Cited by 253
Human GRIN2B variants in neurodevelopmental disorders
Hu, C., Chen, W., Myers, S. J., Yuan, H., & Traynelis, S. F. (2016) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2016.10.002 · Cited by 239
Genetics of intellectual disability in consanguineous families
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
Genetics and genomics of autism spectrum disorder: embracing complexity
De Rubeis, S., & Buxbaum, J. D. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv273 · Cited by 208
Effectiveness of whole-exome sequencing and costs of the traditional diagnostic trajectory in children with intellectual disability
Monroe, G. R., Frederix, G., Savelberg, S. M. C., de Vries, T. I., Duran, K. J., van der Smagt, J. J., Terhal, P. A., van Hasselt, P. M., Kroes, H. Y., Verhoeven‐Duif, N. M., et al. (2016) · Genetics in Medicine · doi:10.1038/gim.2015.200 · Cited by 188
Targeted Next‐Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability
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
From Structure to Phenotype: Impact of Collagen Alterations on Human Health
Arseni, L., Lombardi, A., & Orioli, D. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051407 · Cited by 186
“Normal growth parameters and no evident dysmorphism are recorded in adults [121,122].”
Background
An expanded sequence context model broadly explains variability in polymorphism levels across the human genome
Aggarwala, V., & Voight, B. F. (2016) · Nature Genetics · doi:10.1038/ng.3511 · Cited by 189
Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families
Harripaul, 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
Transcript expression-aware annotation improves rare variant interpretation
Cummings, B. B., Karczewski, K. J., Kosmicki, J. A., Seaby, E. G., Watts, N. A., Singer‐Berk, M., Mudge, J. M., Karjalainen, J. M., Satterstrom, F. K., O’Donnell‐Luria, A., et al. (2020) · Nature · doi:10.1038/s41586-020-2329-2 · Cited by 181
Mechanistic Insight into NMDA Receptor Dysregulation by Rare Variants in the GluN2A and GluN2B Agonist Binding Domains
Swanger, S. A., Chen, W., Wells, G., Burger, P. B., Tankovic, A., Bhattacharya, S., Strong, K. L., Hu, C., Kusumoto, H., Zhang, J., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.10.002 · Cited by 183
Syndromic autism spectrum disorders: moving from a clinically defined to a molecularly defined approach
Fernandez, B. A., & Scherer, S. W. (2017) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2017.19.4/sscherer · Cited by 169
A novel rasopathy caused by recurrent de novo missense mutations in PPP1CB closely resembles Noonan syndrome with loose anagen hair
Gripp, K. W., Aldinger, K. A., Bennett, J. T., Baker, L., Tusi, J., Powell‐Hamilton, N., Stabley, D. L., Sol‐Church, K., Timms, A. E., & Dobyns, W. B. (2016) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.37781 · Cited by 152
Distinct roles of GRIN2A and GRIN2B variants in neurological conditions
Myers, S. J., Yuan, H., Kang, J., Tan, F. C. K., Traynelis, S. F., & Low, C. (2019) · F1000Research · doi:10.12688/f1000research.18949.1 · Cited by 151
Genetic and Epigenetic Etiology Underlying Autism Spectrum Disorder
Yoon, S. H., Choi, J., Lee, W. Y., & Do, J. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9040966 · Cited by 175
Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease
Johnson, M. R., Shkura, K., Langley, S. R., Delahaye‐Duriez, A., Srivastava, P. K., Hill, W. D., Rackham, O. J. L., Davies, G., Harris, S. E., Moreno‐Moral, A., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4205 · Cited by 140
Glutamatergic synapses in neurodevelopmental disorders
Moretto, E., Murru, L., Martano, G., Sassone, J., & Passafaro, M. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.09.014 · Cited by 146
De novo mutations and rare variants occurring in NMDA receptors
XiangWei, W., Jiang, Y., & Yuan, H. (2017) · Current Opinion in Physiology · doi:10.1016/j.cophys.2017.12.013 · Cited by 133
The Psychiatric Cell Map Initiative: A Convergent Systems Biological Approach to Illuminating Key Molecular Pathways in Neuropsychiatric Disorders
Willsey, A. J., Morris, M. T., Wang, S., Willsey, H. R., Sun, N., Teerikorpi, N., Baum, T., Cagney, G., Bender, K. J., Desai, T. A., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.016 · Cited by 129
Expansion and concatenation of nonmuscle myosin IIA filaments drive cellular contractile system formation during interphase and mitosis
Fenix, A. M., Taneja, N., Buttler, C. A., Lewis, J. H., van Engelenburg, S. B., Ohi, R., & Burnette, D. T. (2016) · Molecular Biology of the Cell · doi:10.1091/mbc.e15-10-0725 · Cited by 118
De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis
Wang, S., Mandell, J. D., Kumar, Y., Sun, N., Morris, M. T., Arbelaez, J., Nasello, C., Dong, S., Duhn, C., Zhao, X., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.08.082 · Cited by 120
Structure, functions and regulation of CERT, a lipid‐transfer protein for the delivery of ceramide at the ER–Golgi membrane contact sites
Kumagai, K., & Hanada, K. (2019) · FEBS Letters · doi:10.1002/1873-3468.13511 · Cited by 125
Mutations in GABRB3
Møller, R. S., Wuttke, T. V., Helbig, I., Marini, C., Johannesen, K. M., Brilstra, E. H., Vaher, U., Borggraefe, I., Talvik, I., Talvik, T., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000003565 · Cited by 119
SYNGAP1: Mind the Gap
Jeyabalan, N., & Clement, J. P. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00032 · Cited by 130
Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU
Study, D., Depienne, C., Nava, C., Keren, B., Heide, S., Rastetter, A., Passemard, S., Chantot‐Bastaraud, S., Moutard, M., Agrawal, P. B., et al. (2017) · Human Genetics · doi:10.1007/s00439-017-1772-0 · Cited by 114
Protein phosphatases in the regulation of mitosis
Nilsson, J. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201809138 · Cited by 117
Anatomy of four human Argonaute proteins
Nakanishi, K. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac519 · Cited by 116
Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders
Gillentine, M. A., Wang, T., Hoekzema, K., Rosenfeld, J. A., Liu, P., Guo, H., Kim, C. N., Vries, B. B. A. D., Vissers, L. E. L. M., Nordenskjöld, M., et al. (2021) · Genome Medicine · doi:10.1186/s13073-021-00870-6 · Cited by 113
Identification of Intellectual Disability Genes in Female Patients with a Skewed X-Inactivation Pattern
Fieremans, N., Esch, H. V., Holvoet, M., Goethem, G. V., Devriendt, K., Rosello, M., Mayo, S., Martı́nez, F., Jhangiani, S. N., Muzny, D. M., et al. (2016) · Human Mutation · doi:10.1002/humu.23012 · Cited by 108
SHOC2–MRAS–PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis
Young, L. C., Hartig, N., Boned del Río, I., Sari, S., Ringham-Terry, B., Wainwright, J. R., Jones, G. G., McCormick, F., & Rodriguez-Viciana, P. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1720352115 · Cited by 98
Disruption of TCF4 regulatory networks leads to abnormal cortical development and mental disabilities
Li, H., Zhu, Y., Morozov, Y. M., Chen, X., Page, S. C., Rannals, M. D., Maher, B. J., & RAKIC, P. T. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0353-0 · Cited by 97
Decrease of SYNGAP1 in GABAergic cells impairs inhibitory synapse connectivity, synaptic inhibition and cognitive function
Berryer, M. H., Chattopadhyaya, B., Xing, P., Riebe, I., Bosoi, C., Sanon, N., Antoine-Bertrand, J., Lévesque, M., Avoli, M., Hamdan, F. F., et al. (2016) · Nature Communications · doi:10.1038/ncomms13340 · Cited by 93
Self-citation
Arc Requires PSD95 for Assembly into Postsynaptic Complexes Involved with Neural Dysfunction and Intelligence
Fernández, E., Collins, M. O., Frank, R., Zhu, F., Kopanitsa, M. V., Nithianantharajah, J., Lemprière, S. A., Fricker, D. G., Elsegood, K. A., McLaughlin, C. L., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.045 · Cited by 91
Synaptic clustering differences due to different GABRB3 mutations cause variable epilepsy syndromes
Shi, Y., Zhang, Q., Cai, K., Poliquin, S., Shen, W., Winters, N. D., Yi, Y., Wang, J., Hu, N., Macdonald, R. L., et al. (2019) · Brain · doi:10.1093/brain/awz250 · Cited by 92
Heterozygous HNRNPU variants cause early onset epilepsy and severe intellectual disability
Bramswig, N. C., Lüdecke, H., Hamdan, F. F., Altmüller, J., Beleggia, F., Elcioglu, N. H., Freyer, C., Gerkes, E. H., Demirkol, Y. K., Knupp, K. G., et al. (2017) · Human Genetics · doi:10.1007/s00439-017-1795-6 · Cited by 86
Self-citation
Redefining the MED13L syndrome
Adegbola, A. A., Musante, L., Callewaert, B. L., Maciel, P., Hu, H., Isidor, B., Picker‐Minh, S., Caignec, C. L., Chiaie, B. D., Vanakker, O. M., et al. (2015) · European Journal of Human Genetics · doi:10.1038/ejhg.2015.26 · Cited by 88
Rare and common epilepsies converge on a shared gene regulatory network providing opportunities for novel antiepileptic drug discovery
Delahaye‐Duriez, A., Srivastava, P. K., Shkura, K., Langley, S. R., Laaniste, L., Moreno‐Moral, A., Danis, B., Mazzuferi, M., Foerch, P., Gazina, E. V., et al. (2016) · Genome biology · doi:10.1186/s13059-016-1097-7 · Cited by 90
Loss-of-function variants of SCN8A in intellectual disability without seizures
Wagnon, J. L., Barker, B. S., Ottolini, M., Park, Y., Volkheimer, A. D., Valdez, P. T., Swinkels, M. E. M., Patel, M. K., & Meisler, M. H. (2017) · Neurology Genetics · doi:10.1212/nxg.0000000000000170 · Cited by 87
Essential genetic findings in neurodevelopmental disorders
Cardoso, A. R., Lopes‐Marques, M., Silva, R. M., Serrano, C., Amorim, A., Prata, M. J., & Azevedo, L. (2019) · Human Genomics · doi:10.1186/s40246-019-0216-4 · Cited by 99
Chromatin Remodeling Complex NuRD in Neurodevelopment and Neurodevelopmental Disorders
Hoffmann, A., & Spengler, D. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00682 · Cited by 92
Mutations in MBOAT7 , Encoding Lysophosphatidylinositol Acyltransferase I, Lead to Intellectual Disability Accompanied by Epilepsy and Autistic Features
Johansen, A., Rosti, R. Ö., Musaev, D., Sticca, E., Harripaul, R., Zaki, M. S., Çağlayan, A. O., Azam, M., Sultan, T., Froukh, T. J., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.07.019 · Cited by 82
Elucidation of the phenotypic spectrum and genetic landscape in primary and secondary microcephaly
Boonsawat, P., Joset, P., Steindl, K., Oneda, B., Gogoll, L., Azzarello‐Burri, S., Sheth, F. J., Datar, C. A., Verma, I. C., Puri, R. D., et al. (2019) · Genetics in Medicine · doi:10.1038/s41436-019-0464-7 · Cited by 86
TDP-43 Promotes Neurodegeneration by Impairing Chromatin Remodeling
Berson, A., Sartoris, A., Nativio, R., Deerlin, V. M. V., Toledo, J. B., Porta, S., Liu, S., Chung, C., Garcia, B. A., Lee, V. M. ‐., et al. (2017) · Current Biology · doi:10.1016/j.cub.2017.10.024 · Cited by 90
Spectrum of GABAA receptor variants in epilepsy
Maljevic, S., Møller, R. S., Reid, C. A., Pérez‐Palma, E., Lal, D., May, P., & Lerche, H. (2019) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000657 · Cited by 85
Targeted sequencing of 351 candidate genes for epileptic encephalopathy in a large cohort of patients
de Kovel, C. G. F., Brilstra, E. H., van Kempen, M. J. A., Slot, R. V. ‘., Nijman, I. J., Afawi, Z., Jonghe, P. D., Djémié, T., Guerrini, R., Hardies, K., et al. (2016) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.235 · Cited by 84
Molecular and clinical descriptions of patients with GABAA receptor gene variants ( GABRA1 , GABRB2 , GABRB3 , GABRG2 ): A cohort study, review of literature, and genotype–phenotype correlation
Maillard, P., Baer, S., Schaefer, É., Desnous, B., Villeneuve, N., Lepine, A. F., Fabre, A., Lacoste, C., Chehadeh, S. E., Piton, A., et al. (2022) · Epilepsia · doi:10.1111/epi.17336 · Cited by 84
Wiedemann‐Steiner syndrome as a major cause of syndromic intellectual disability: A study of 33 French cases
Baer, S., Afenjar, A., Smol, T., Piton, A., Gérard, B., Alembik, Y., Bienvenu, T., Boursier, G., Boute, O., Colson, C., et al. (2018) · Clinical Genetics · doi:10.1111/cge.13254 · Cited by 81
Spatial genome organization and cognition
Rajarajan, P., Espeso‐Gil, S., Brennand, K., & Akbarian, S. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.124 · Cited by 83
Chd2 Is Necessary for Neural Circuit Development and Long-Term Memory
Kim, Y. J., Khoshkhoo, S., Frankowski, J. C., Zhu, B., Abbasi, S., Lee, S., Wu, Y. E., & Hunt, R. F. (2018) · Neuron · doi:10.1016/j.neuron.2018.09.049 · Cited by 81
GABRB3 mutations: a new and emerging cause of early infantile epileptic encephalopathy
Papandreou, A., McTague, A., Trump, N., Ambegaonkar, G., Ngoh, A., Meyer, E., Scott, R. H., & Kurian, M. A. (2016) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.12976 · Cited by 79
De novo variants in SETD1B are associated with intellectual disability, epilepsy and autism
Hiraide, T., Nakashima, M., Yamoto, K., Fukuda, T., Kato, M., Ikeda, H., Sugie, Y., Aoto, K., Kaname, T., Nakabayashi, K., et al. (2018) · Human Genetics · doi:10.1007/s00439-017-1863-y · Cited by 75
Enrichment of mutations in chromatin regulators in people with Rett syndrome lacking mutations in MECP2
Sajan, S. A., Jhangiani, S. N., Muzny, D. M., Gibbs, R. A., Lupski, J. R., Glaze, D. G., Kaufmann, W. E., Skinner, S. A., Annese, F., Friez, M. J., et al. (2016) · Genetics in Medicine · doi:10.1038/gim.2016.42 · Cited by 81
De novo mutations from whole exome sequencing in neurodevelopmental and psychiatric disorders: From discovery to application
Wang, W., Corominas, R., & Lin, G. N. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00258 · Cited by 70
Protein phosphatase 2A – structure, function and role in neurodevelopmental disorders
Sandal, P., Jong, C. J., Merrill, R. A., Song, J., & Strack, S. (2021) · Journal of Cell Science · doi:10.1242/jcs.248187 · Cited by 76
Genome-wide analysis of differential RNA editing in epilepsyPreprint
Srivastava, P. K., Bagnati, M., Delahaye‐Duriez, A., Ko, J., Rotival, M., Langley, S. R., Shkura, K., Mazzuferi, M., Danis, B., van Eyll, J. M., et al. (2017) · Genome Research · doi:10.1101/gr.210740.116 · Cited by 79
The Genetics of Intellectual Disability
Jansen, S., Vissers, L. E. L. M., & de Vries, B. B. A. (2023) · Brain Sciences · doi:10.3390/brainsci13020231 · Cited by 81
De Novo Truncating Mutations in the Last and Penultimate Exons of PPM1D Cause an Intellectual Disability Syndrome
Jansen, S., Geuer, S., Pfundt, R., Brough, R., Ghongane, P., Herkert, J. C., Marco, E. J., Willemsen, M. H., Kleefstra, T., Hannibal, M., et al. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.02.005 · Cited by 75
De Novo Mutations in PPP3CA Cause Severe Neurodevelopmental Disease with Seizures
Myers, C. T., Stong, N., Mountier, E. I., Helbig, K. L., Freytag, S., Sullivan, J. E., Zeev, B. B., Nissenkorn, A., Tzadok, M., Heimer, G., et al. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.08.013 · Cited by 72
Whole genome sequencing provides better diagnostic yield and future value than whole exome sequencing
Mattick, J. S., Dinger, M. E., Schönrock, N., & Cowley, M. J. (2018) · The Medical Journal of Australia · doi:10.5694/mja17.01176 · Cited by 69
A Rare Variant Identified Within the GluN2B C-Terminus in a Patient with Autism Affects NMDA Receptor Surface Expression and Spine Density
Liu, S., Zhou, L., Yuan, H., Vieira, M., Sanz-Clemente, A., Badger, J. D., Lu, W., Traynelis, S. F., & Roche, K. W. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.0827-16.2017 · Cited by 69
Spatial centrosome proteome of human neural cells uncovers disease-relevant heterogeneity
O’Neill, A. C., Uzbaş, F., Antognolli, G., Merino, F., Draganova, K., Jäck, A., Zhang, S., Pedini, G., Schessner, J. P., Cramer, K., et al. (2022) · Science · doi:10.1126/science.abf9088 · Cited by 71
Intragenic FMR1 disease-causing variants: a significant mutational mechanism leading to Fragile-X syndrome
Quartier, A., Poquet, H., Gilbert‐Dussardier, B., Rossi, M., Casteleyn, A.-S., Portes, V. D., Feger, C., Nourisson, E., Kuentz, P., Redin, C. E., et al. (2017) · European Journal of Human Genetics · doi:10.1038/ejhg.2016.204 · Cited by 68
WDR45 , one gene associated with multiple neurodevelopmental disorders
Cong, Y., So, V., Tijssen, M. A. J., Verbeek, D. S., Reggiori, F., & Mauthe, M. (2021) · Autophagy · doi:10.1080/15548627.2021.1899669 · Cited by 72
Gene4Denovo: an integrated database and analytic platform for de novo mutations in humans
Zhao, G., Li, K., Li, B., Wang, Z., Fang, Z., Wang, X., Zhang, Y., Luo, T., Zhou, Q., Wang, L., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz923 · Cited by 64
Chromatin Remodeling Proteins in Epilepsy: Lessons From CHD2-Associated Epilepsy
Lamar, K., & Carvill, G. L. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00208 · Cited by 69
Switching modes in corticogenesis: mechanisms of neuronal subtype transitions and integration in the cerebral cortex
Toma, K., & Hanashima, C. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00274 · Cited by 74
A Gain-of-Function Mutation inNALCNin a Child with Intellectual Disability, Ataxia, and Arthrogryposis
Aoyagi, K., Rossignol, E., Hamdan, F. F., Mulcahy, B., Xie, L., Nagamatsu, S., Rouleau, G. A., Zhen, M., & Michaud, J. L. (2015) · Human Mutation · doi:10.1002/humu.22797 · Cited by 65
Self-citation
Genome-wide DNA methylation meta-analysis in the brains of suicide completers
Policicchio, S., Washer, S., Viana, J., Iatrou, A., Burrage, J., Hannon, E., Turecki, G., Kaminsky, Z., Mill, J., Dempster, E. L., et al. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0752-7 · Cited by 61
Increased diagnostic and new genes identification outcome using research reanalysis of singleton exome sequencing
Bruel, A., Nambot, S., Quéré, V., Vitobello, A., Thévenon, J., Assoum, M., Moutton, S., Houcinat, N., Lehalle, D., Jean‐Marçais, N., et al. (2019) · European Journal of Human Genetics · doi:10.1038/s41431-019-0442-1 · Cited by 62
A targeted resequencing gene panel for focal epilepsy
Hildebrand, M. S., Myers, C. T., Carvill, G. L., Regan, B. M., Damiano, J. A., Mullen, S. A., Newton, M. R., Nair, U., Gazina, E. V., Milligan, C. J., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000002608 · Cited by 61
Control of Neuronal Development by T-Box Genes in the Brain
Mihalas, A. B., & Hevner, R. F. (2016) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2016.08.001 · Cited by 61
Varying Intolerance of Gene Pathways to Mutational Classes Explain Genetic Convergence across Neuropsychiatric Disorders
Shohat, S., Ben‐David, E., & Shifman, S. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.02.007 · Cited by 58
Impact of clinical exomes in neurodevelopmental and neurometabolic disorders
Evers, C., Staufner, C., Granzow, M., Paramasivam, N., Hinderhofer, K., Kaufmann, L. T., Fischer, C., Thiel, C., Opladen, T., Kotzaeridou, U., et al. (2017) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2017.06.014 · Cited by 57
A genotype-first approach identifies an intellectual disability-overweight syndrome caused by PHIP haploinsufficiency
Jansen, S., Hoischen, A., Coe, B. P., Carvill, G. L., Esch, H. V., Bosch, D. G. M., Andersen, U. A., Baker, C. A., Bauters, M., Bernier, R., et al. (2017) · European Journal of Human Genetics · doi:10.1038/s41431-017-0039-5 · Cited by 64
Dysregulation of Neurite Outgrowth and Cell Migration in Autism and Other Neurodevelopmental Disorders
Prem, S., Millonig, J. H., & DiCicco-Bloom, E. M. (2020) · Advances in neurobiology · doi:10.1007/978-3-030-45493-7_5 · Cited by 59
Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures
Tang, S. S., Addis, L., Smith, A. B., Topp, S. D., Pendziwiat, M., Mei, D., Parker, A. P. J., Agrawal, S., Hughes, E., Lascelles, K., et al. (2020) · Epilepsia · doi:10.1111/epi.16508 · Cited by 61
Ceramide signalling in inherited and multifactorial brain metabolic diseases
Pant, D. C., Aguilera, S., & Pujol, A. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105014 · Cited by 56
Core autophagy genes and human diseases
Zhao, Y. G., & Zhang, H. (2019) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2019.08.003 · Cited by 55
Surface Expression, Function, and Pharmacology of Disease-Associated Mutations in the Membrane Domain of the Human GluN2B Subunit
Vyklický, V., Krausová, B. H., Černý, J., Ladislav, M., Smejkalová, T., Kysilov, B., Kořı́nek, M., Danačíková, Š., Hořák, M., Chodounská, H., et al. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00110 · Cited by 54
AUTS2 isoforms control neuronal differentiation
Monderer‐Rothkoff, G., Tal, N., Risman, M., Shani, O., Nissim‐Rafinia, M., Malki-Feldman, L., Medvedeva, V. P., Groszer, M., Meshorer, E., & Shifman, S. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0409-1 · Cited by 57
Heterogeneous nuclear ribonucleoprotein U (HNRNPU) safeguards the developing mouse cortex
Sapir, T., Kshirsagar, A., Gorelik, A., Olender, T., Porat, Z., Scheffer, I. E., Goldstein, D. B., Devinsky, O., & Reiner, O. (2022) · Nature Communications · doi:10.1038/s41467-022-31752-z · Cited by 54
WAC loss-of-function mutations cause a recognisable syndrome characterised by dysmorphic features, developmental delay and hypotonia and recapitulate 10p11.23 microdeletion syndrome
DeSanto, C. L., D׳Aco, K., Araujo, G. C., Shannon, N. L., Study, D., Vernon, H. J., Rahrig, A., Monaghan, K. G., Niu, Z., Vitazka, P., et al. (2015) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2015-103069 · Cited by 58
De novo mutations in HNRNPU result in a neurodevelopmental syndrome
Yates, T. M., Vasudevan, P. C., Chandler, K., Donnelly, D. E., Stark, Z., Sadedin, S., Willoughby, J., Study, D., & Balasubramanian, M. (2017) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.38492 · Cited by 54
Regulation of Synaptic Transmission and Plasticity by Protein Phosphatase 1
Foley, K., McKee, C., Nairn, A. C., & Xia, H. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.2026-20.2021 · Cited by 56
Brain-specific transcriptional regulator T-brain-1 controls brain wiring and neuronal activity in autism spectrum disorders
Huang, T., & Hsueh, Y. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00406 · Cited by 54
Bridging the Gap between Genes and Language Deficits in Schizophrenia: An Oscillopathic Approach
Murphy, E., & Benítez‐Burraco, A. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00422 · Cited by 53

Authors: Hamdan, F. F., Srour, M., Capo-Chichi, J.-M., Daoud, H., Nassif, C., Patry, L., Massicotte, C., Ambalavanan, A., Spiegelman, D., Diallo, O., Henrion, E., Dionne-Laporte, A., Fougerat, A., Pshezhetsky, A. V., Venkateswaran, S., Rouleau, G. A., & Michaud, J. L.
Affiliations: CHU Sainte-Justine Research Center (CA)
Montreal Children's Hospital (CA)
Montreal Neurological Institute and Hospital (CA)
Children's Hospital of Eastern Ontario (CA)
Corresponding author: Michaud, Jacques L.
ORCID: Hamdan, Fadi F.
Srour, Myriam
Daoud, Hussein
Ambalavanan, Amirthagowri
Spiegelman, Dan
Fougerat, Anne
Pshezhetsky, Alexey V.
Rouleau, Guy A.
Michaud, Jacques L.
Venue: PLoS Genetics
Publisher: Public Library of Science (PLoS)
Published: 2014-10-30
Volume: 10
Issue: 10
Pages: e1004772
ISSN: 1553-7390 (ISSN-L)
1553-7404
DOI: 10.1371/journal.pgen.1004772
PMC: PMC4214635
OpenAlex: W2058423880
Cited by: 419
References: 62
Citations by year: 2026: 18 · 2025: 27 · 2024: 23 · 2023: 27 · 2022: 39 · 2021: 45 · 2020: 33 · 2019: 43 · 2018: 52 · 2017: 49 · 2016: 43 · 2015: 20
FWCI: 24.22
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS Genetics (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
HAL (submittedVersion, cc-by)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
eScholarship@McGill (McGill) (submittedVersion)
Figshare (submittedVersion, cc-by)
Funders: McGill University
Canadian Institutes of Health Research
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
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
Keywords: de novo mutations, intellectual disability, exome sequencing, loss-of-function mutations, single nucleotide substitution, ARID1B, CHD2, FOXG1, GABRB3, NR2B subunit, MBD5, MED13L, SETBP1, Tbr1, TCF4, WDR45, protein network analysis, diagnostic yield, pathogenic variants
MeSH terms: Epilepsy, Humans, Intellectual Disability, RNA Splicing, Frameshift Mutation, Point Mutation, Sequence Deletion, Codon, Nonsense, Mutation, Missense, Exome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

De Novo Mutations in Moderate or Severe Intellectual Disability

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks