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

Items 301–400 of 418

GABA(A) Receptor Subunit (γ2, δ, β1-3) Variants in Genetic Epilepsy: A Comprehensive Summary of 206 Clinical Cases
Zhu, X., & Li, P. (2024) · Journal of Child Neurology · doi:10.1177/08830738241273437 · Cited by 4
Identifying SETBP1 haploinsufficiency molecular pathways to improve patient diagnosis using induced pluripotent stem cells and neural disease modelling
Shaw, N. C., Chen, K., Farley, K. O., Hedges, M. G., Forbes, C. A., Baynam, G. S., Lassmann, T., & Fear, V. S. (2024) · Molecular Autism · doi:10.1186/s13229-024-00625-1 · Cited by 4
Expanding the phenotype of PURA-related neurodevelopmental disorder: a close differential diagnosis of infantile hypotonia with psychomotor retardation and characteristic facies
Mishra, S., Girisha, K. M., & Shukla, A. (2020) · Clinical Dysmorphology · doi:10.1097/mcd.0000000000000360 · Cited by 4
Complex congenital cardiovascular anomaly in a patient with AGO1 ‐associated disorder
Takagi, M., Ono, S., Kumaki, T., Nishimura, N., Murakami, H., Enomoto, Y., Naruto, T., Ueda, H., & Kurosawa, K. (2022) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.63089 · Cited by 4
Organelle contacts: Sub‐organelle zones to facilitate rapid and accurate inter‐organelle trafficking of lipids
Hanada, K. (2019) · Traffic · doi:10.1111/tra.12716 · Cited by 4
Whole‑exome sequencing study identifies two novel rare variations associated with congenital talipes equinovarus
Zhang, J., Li, S., Ma, S., Liu, Y., Wang, X., & Li, Y. (2020) · Molecular Medicine Reports · doi:10.3892/mmr.2020.11038 · Cited by 4
Targeted next-generation sequencing identifies the disruption of the SHANK3 and RYR2 genes in a patient carrying a de novo t(1;22)(q43;q13.3) associated with signs of Phelan-McDermid syndrome
Bonaglia, M. C., Bertuzzo, S., Ciaschini, A. M., Discepoli, G., Castiglia, L., Romaniello, R., Zuffardi, O., & Fichera, M. (2020) · Molecular Cytogenetics · doi:10.1186/s13039-020-00490-6 · Cited by 4
The Identification of Proteolytic Substrates of Calpain-5 with N-Terminomics
Gál, J., Dufour, A., Young, D. W., Yang, E. S.-H., & Geddes, J. W. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26136459 · Cited by 3
Further delineation of SET ‐related intellectual disability syndrome
Shono, K., Enomoto, Y., Tsurusaki, Y., Kumaki, T., Masuno, M., & Kurosawa, K. (2022) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.62681 · Cited by 3
The MED13L Foundation strategic research plan: a roadmap to the future
Heilmann, R., Pfalzer, A. C., Bichell, T. J., Terala, A., Campbell, A. N., Taatjes, D. J., Ghoumid, J., Grueter, C. E., Bain, J., Strich, R., et al. (2024) · Therapeutic Advances in Rare Disease · doi:10.1177/26330040241290252 · Cited by 3
Prenatal diagnosis and molecular cytogenetic characterization of a chromosome 1q42.3-q44 deletion in a fetus associated with ventriculomegaly on prenatal ultrasound
Chen, C., Ko, T., Wang, L., Chern, S., Wu, P.-S., Chen, S.-W., Wu, F.-T., Chen, Y., Chen, W.-L., & Wang, W. (2020) · Taiwanese Journal of Obstetrics and Gynecology · doi:10.1016/j.tjog.2020.05.022 · Cited by 3
Novel MYH10 heterozygous variants associated to a syndrome combining mainly ptosis and ocular coloboma expand the MYH10 related phenotypes
Scheidecker, S., Bär, S., Kröll‐Hermi, A., Delvallée, C., Rinaldi, B., Korpioja, A., Geoffroy, V., Schaefer, É., Secula, S., Jaeger, C., et al. (2025) · European Journal of Human Genetics · doi:10.1038/s41431-025-01803-2 · Cited by 3
The epigenetics of autism
Massrali, A., Warrier, V., Paul, A., Adhya, D., Srivastava, D. P., Kotter, M., & Baron‐Cohen, S. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813796-3.00013-4 · Cited by 3
GRIN2A and GRIN2B and Their Related Phenotypes
Sapuppo, A., Portale, L., Massimino, C. R., Presti, S., Tardino, L. G., Marino, S. D., Polizzi, A., Falsaperla, R., & Praticò, A. D. (2021) · Journal of Pediatric Neurology · doi:10.1055/s-0041-1727146 · Cited by 3
Doctor of Philosophy (PhD)
Biss, M. (2015) · Cited by 3
Systematic functional characterization of the intellectual disability-associated SWI/SNF complex reveals distinct roles for the BAP and PBAP complexes in post-mitotic memory forming neurons of the Drosophila mushroom bodyPreprint
Chubak, M. C., Stone, M. H., Raun, N., Rice, S. L., Sarikahya, M. H., Jones, S. G., Lyons, T. A., Jakub, T. E., Mainland, R. L., Knip, M. J., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/408500 · Cited by 3
A genome-wide association study identifies novel genetic variants associated with neck or shoulder pain in the UK biobank (N = 430,193)
Tao, Y., Pan, Q., Cai, T., Lu, Z. H., Haque, M., Dottorini, T., Colvin, L., Smith, B. H., & Meng, W. (2025) · PAIN Reports · doi:10.1097/pr9.0000000000001267 · Cited by 2
Multiple Integration and Data Annotation Study (MIDAS): improving next-generation sequencing data analysis by genotype-phenotype correlations
Dincer, Y., Schulz, J., Wilson, S., Marschall, C., Cohen, M. Y., Mall, V., Klein, H., & Eck, S. H. (2018) · Journal of Laboratory Medicine · doi:10.1515/labmed-2017-0072 · Cited by 1
Revisiting the neutral dynamics derived limiting guanine-cytosine content using human de novo point mutation data
Li, W., Almirantis, Y., & Provata, A. (2021) · Meta Gene · doi:10.1016/j.mgene.2021.100994 · Cited by 2
Introduction of a de novo Creb-binding protein gene mutation in sperm to produce a Rubinstein-Taybi syndrome model using inbred C57BL/6 mice
Takagi, T., Higashi, Y., Asai, M., & Ishii, S. (2020) · Brain Research · doi:10.1016/j.brainres.2020.147140 · Cited by 2
Global developmental delay and intellectual disability
Srour, M., AlHakeem, A., & Shevell, M. I. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813955-4.00019-2 · Cited by 2
Self-citation
Expression analyses of WAC, a responsible gene for neurodevelopmental disorders, during mouse brain development
Nishikawa, M., Matsuki, T., Hamada, N., Nakayama, A., Ito, H., & Nagata, K. (2023) · Medical Molecular Morphology · doi:10.1007/s00795-023-00364-x · Cited by 2
GRIN2B-related neurodevelopmental disorders: genotype-phenotype correlations and therapeutic implications
Xie, C., Kessi, M., Liu, F., He, F. P., & Peng, J. (2025) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-025-04055-x · Cited by 2
Haploinsufficiency of AKT3 gene causing microcephaly and psychomotor delay in a patient with 1q43q44 microdeletion
Pelle, A., Modena, P., Cavallini, A. R., & Selicorni, A. (2020) · Clinical Dysmorphology · doi:10.1097/mcd.0000000000000313 · Cited by 2
The Pitt-Hopkins Syndrome: Report of 5 Patients and Literature Comparison
Kutluk, G., Kadem, E. N., Randa, N. C., & Öz, A. (2021) · Acta Medica Alanya · doi:10.30565/medalanya.891840 · Cited by 2
Primary complex motor stereotypies are associated with de novo damaging DNA coding mutations that identify candidate risk genes and biological pathwaysPreprint
Fernandez, T. V., Williams, Z. P., Kline, T., Rajendran, S., Augustine, F., Wright, N. R. D., Sullivan, C. A. W., Olfson, E., Abdallah, S. B., Liu, W., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/730952 · Cited by 2
PP1β opposes classic PP1 function, inhibiting spine maturation and promoting LTPPreprint
Foley, K., McKee, C., Mayer, A., Ganguly, A., Barnett, D., Ward, N., Zhang, Y., Nairn, A. C., & Xia, H. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.26.525737 · Cited by 2
Complementary vertebrate Wac models exhibit phenotypes relevant to DeSanto-Shinawi SyndromePreprint
Lee, K., Stafford, A. M., Pacheco-Vergara, M., Cichewicz, K., Canales, C. P., Seban, N., Corea, M., Rahbarian, D., Bonekamp, K. E., Gillie, G. R., et al. (2025) · eLife · doi:10.7554/elife.109104 · Cited by 2
The emerging face of FOXG1 Syndrome: a rare, genetically defined neurodevelopmental disorder coming of age in the genomics era.Preprint
Mueller, K., Shine, M. G., Lee, J. W., Lee, S., & Malone, K. E. (2024) · Research Square · doi:10.21203/rs.3.rs-4949811/v1 · Cited by 2
Alterations in background ECoG activity and behavioral deficits in a mouse model of CHD2-related developmental delayPreprint
Mavashov, A., Turk, S., Sarusi, Y., Brusel, M., Perry, R. B., Quinn, S., Almog, Y., Vilian, K., Ulitsky, I., & Rubinstein, M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.18.643778 · Cited by 2
Prenatal diagnosis of a de novo 10p12.1p11.23 microdeletion encompassing the WAC gene in a fetus associated with bilateral hydronephrosis and right clubfoot on prenatal ultrasound
Chen, C., Chen, C., Wu, F.-T., Pan, Y.-T., Wu, P.-S., & Wang, W. (2024) · Taiwanese Journal of Obstetrics and Gynecology · doi:10.1016/j.tjog.2024.05.008 · Cited by 1
GPBP or CERT: The Roles in Autoimmunity, Cancer or Neurodegenerative Disease—A Systematic Review
Vivó, P., Hernández‐Andreu, J. M., Prieto-Ruiz, J. Á., & Ventura, I. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252313179 · Cited by 1
Classifying Gaze Patterns for Preemptive Screening of Autism Spectrum Disorder (ASD) in Children Using Deep Learning
Dhruva, G., Bhat, I., & Sivagamasundari, G. (2025) · International Conference on Innovative Trends in Information Technology (ICITIIT) · doi:10.1109/icitiit64777.2025.11040981 · Cited by 1
Complete commissural agenesis in a child with Noonan-like syndrome with loose anagen hair 2
Gana, S., Piccinni, L., Rognone, E., Beverino, A., Varesio, C., Asaro, A., Pichiecchio, A., & Valente, E. M. (2025) · Neurogenetics · doi:10.1007/s10048-025-00832-9 · Cited by 1
A Novel Intronic Mutation in MBD5 Results in Autosomal Dominant Intellectual Disability Type 1 due to Abnormal Splicing
Jiang, H., Mou, J., Zhao, Q., Ding, L., Wang, Y., Guo, X., & Yang, G. (2025) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.70121 · Cited by 1
Novel Intragenic Duplication of GATAD2B in a Patient With GAND
Mori, M., Estes, S., Ramadesikan, S., Schmalz, B., Plourde, S. M., Hernandez‐Gonzalez, M. E., Miller, A. R., Chaudhari, B. P., Wilson, R. K., & Koboldt, D. C. (2025) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.64205 · Cited by 1
Structural basis of nonmuscle myosin-2 autoinhibition mechanisms
Heissler, S. M., Grandinetti, G., Sellers, J. R., & Chinthalapudi, K. (2026) · Nature Communications · doi:10.1038/s41467-026-74674-w · Cited by 1
Single-cell RNA and ATAC sequencing reveals cell subsets characteristics in adipose-derived stem cells
Long, Q., Yuan, Y., Liu, Z., Zhang, P., & Yuan, X. (2026) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2026.159734 · Cited by 2
Multiplex Portuguese families as a lens into rare mutations and the shared genetic architecture of schizophrenia, mood disorders, and autism spectrum disorders
Pato, C. N., Pato, M. T., Mulle, J., Hart, R. P., Pang, Z. P., Knowles, J. A., Singh, T., Maddhesiya, P., Carvalho, C. B., Merikangas, A. K., et al. (2026) · Genomic psychiatry : · doi:10.61373/gp026h.0045 · Cited by 1
Early infantile epileptic encephalopathy type 54: clinical and neurophysiological aspects
I, D. V., & Aysina, V. A. (2021) · Epilepsy and Paroxysmal Conditions · doi:10.17749/2077-8333/epi.par.con.2021.053 · Cited by 1
Tissue-specific DNase I footprint analysis confirms the association of GATAD2B Q470* variant with intellectual disability
Nikam, V., & Naushad, S. M. (2021) · Journal of Genetics · doi:10.1007/s12041-021-01308-z · Cited by 1
Neurochemistry evaluated by magnetic resonance spectroscopy in a patient with FBXO28-related developmental and epileptic encephalopathy
Sano, K., Miya, F., Kato, M., Omata, T., & Takanashi, J. (2023) · Brain and Development · doi:10.1016/j.braindev.2023.07.003 · Cited by 1
Noncoding de novo mutations in SCN2A are associated with autism spectrum disorders
Zhang, Y., Ahsan, M. U., & Wang, K. (2025) · iScience · doi:10.1016/j.isci.2025.113258 · Cited by 2
Experimental Tools for the Identification of Specific Genes in Autism Spectrum Disorders and Intellectual Disability
Shen, Y., & Gong, X. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800109-7.00001-7 · Cited by 1
Les modifications de pratique clinique liées à l’arrivée du séquençage haut débit dans le diagnostic génétique des maladies du développement
Demougeot, L., Houdayer-Robert, F., Pélissier, A., Mohrez, F., Thévenon, J., Duffourd, Y., Nambot, S., Gautier, É., Binquet, C., Rossi, M., et al. (2018) · Archives de Pédiatrie · doi:10.1016/j.arcped.2017.12.006 · Cited by 1
Massive parallel sequencing for molecular-genetic diagnosis of mental retardation
Levchenko, O. A., & Лавров, А. В. (2018) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro201811812165 · Cited by 1
A murine Wac model exhibits phenotypes relevant to DeSanto-Shinawi SyndromePreprint
Stafford, A. M., Pacheco-Vergara, M., Uhl, K. L., Jager, T. E., Li, X., Jeong, J., & Vogt, D. L. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.24.477600 · Cited by 1
Importance of Glutamine in Synaptic Vesicles Revealed by Functional Studies of SLC6A17 and Its Mutations Pathogenic for Intellectual DisabilityPreprint
Jia, X., Zhu, J., Bian, X., Liu, S., Yu, S., Liang, W., Jiang, L., Mao, R., & Rao, Y. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.25.513688 · Cited by 1
Importance of Glutamine in Synaptic Vesicles Revealed by Functional Studies of SLC6A17 and Its Mutations Pathogenic for Intellectual DisabilityPreprint
Jia, X., Zhu, J., Bian, X., Liu, S., Yu, S., Liang, W., Jiang, L., Mao, R., & Rao, Y. (2023) · eLife · doi:10.7554/elife.86972.1 · Cited by 1
Clinical utility of next-generation sequencing in neurodevelopmental disorders: non-syndromic intellectual disability as a model
Çağlayan, A. O. (2015) · Istanbul Bilim University Florence Nightingale Journal of Medicine · doi:10.5606/fng.btd.2015.011
Schizophrenia hiPSC neurons display expression changes that are enriched for disease risk variants and a blunted activity-dependent responsePreprint
Roussos, P., Guennewig, B., Kaczorowski, D. C., Barry, G., & Brennand, K. (2016) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/062885
Paternally Inherited GABRB3 Intragenic Deletion in a Boy with Autistic Features and Angelman Syndrome Phenotype–Case Report and Literature Review
SzczaAuba, K., & Jaszczuk, I. (2016) · Autism - Open Access · doi:10.4172/2165-7890.1000182
Heterozygous STXBP1 Mutations Associated with Ohtahara Syndrome: Two Littles Make a Lot
Nieto‐Estévez, V., & Hsieh, J. (2016) · Epiliepsy currents/Epilepsy currents · doi:10.5698/1535-7511-16.5.330
Identificação da etiologia da deficiência intelectual esporádica por sequenciamento de exomas de afetados e seus pais
Carneiro, T. N. R. (2017) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.41.2017.tde-28032017-153312
Response to Hartley et al. and Mullegama et al.
Tanpaiboon, P., & Chapman, K. A. (2017) · Genetics in Medicine · doi:10.1038/gim.2017.148
Molecular Analysis of Hotspot Regions ofARXandMECP2Genes in Intellectual Disability and Cornelia De Lange Syndrome
Kulkarni, G., & Ranade, S. H. (2017) · International Journal of Human Genetics · doi:10.1080/09723757.2017.1351119
Computational genomics and genetics of developmental disorders
Qi, H. (2018) · doi:10.7916/d8n02qdr
Characterization of high-density prion protein oligomers in rapid progressive and sporadic Alzheimer’s disease
Shafiq, M. (2019) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-7266
Investigação por sequenciamento do exoma completo da etiologia genética da deficiência intelectual familial
da Costa, S. S. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.41.2019.tde-18022019-173017
Integration of Functional Genomic Data in Genetic Analysis
Chen, S. (2021) · doi:10.7916/d8-snjy-r856
Natural Ligand-Mimetic and Nonmimetic Inhibitors of the Ceramide Transport Protein CERT
Hanada, K., Sakai, S., & Kumagai, K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042098
Infantile Developmental Delay Caused by Pathogenic Mutation in WDR45 Gene and Literature ReviewPreprint
Cao, Q., Wang, H., & Huo, L. (2021) · Research Square · doi:10.21203/rs.3.rs-964834/v1
Genetic forms of developmental delay and intellectual disability in the practice of the medical genetic consultation of Research Centre for Medical Genetics
Anisimova, I. V. (2021) · Nauchno-prakticheskii zhurnal «Medicinskaia genetika» · doi:10.25557/2073-7998.2021.07.45-58
Faculty Opinions recommendation of Transcript expression-aware annotation improves rare variant interpretation.
Cobat, A. (2021) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.738024165.793584912
Faculty Opinions recommendation of InterVar: Clinical Interpretation of Genetic Variants by the 2015 ACMG-AMP Guidelines.
Turner, S. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.727251936.793557892
Child with Global Developmental Delay
Flore, L. A., & Campbell, S. (2022) · Springer eBooks · doi:10.1007/978-3-031-10494-7_3
Investigação genética da obesidade sindrômica e desenvolvimento de modelos biológicos para estudo da síndrome de Xia-Gibbs
Carvalho, L. M. L. (2023) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.41.2023.tde-23032023-174554
Supplementary Appendix 1 from High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer
Diets, I. J., Waanders, E., Ligtenberg, M. J. L., van Bladel, D. A. G., Kamping, E. J., Hoogerbrugge, P. M., Hopman, S. M. J., Olderode-Berends, M. J. W., Gerkes, E. H., Koolen, D. A., et al. (2023) · doi:10.1158/1078-0432.22465568
Supplementary Appendix 1 from High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the Cancer Phenotype in Selected Children with Cancer
Diets, I. J., Waanders, E., Ligtenberg, M. J. L., van Bladel, D. A. G., Kamping, E. J., Hoogerbrugge, P. M., Hopman, S. M. J., Olderode-Berends, M. J. W., Gerkes, E. H., Koolen, D. A., et al. (2023) · doi:10.1158/1078-0432.22465568.v1
Epilepsia infantil decorrente de alteração no gene grin2b: um relato de caso
Neto, O. L. D. M., Gonçalves, M. V. L., & de Alencar, C. N. M. (2023) · Revista Neurociências · doi:10.34024/rnc.2023.v31.14759
Prenatal cannabis exposure alters offspring DNA methylation at genes involved in neurodevelopment, across the life coursePreprint
Osborne, A. J., Noble, A. J., Adams, A. T., Satsangi, J. J., & Boden, J. M. (2023) · Research Square · doi:10.21203/rs.3.rs-3183028/v1
Caracterização de CNVS patogênicas em quatro indivíduos do sexo masculino com deficiência intelectual ligada ao X
Henrique, P. P. (2019) · doi:10.47749/t/unicamp.2019.1149394
Whole Exome Sequencing in Intellectual Disability Patients Identifies de novo Mutations in KCNB1, SHANK2, and SYNGAP1 Genes and a Novel Mutation in PPP1R3F
(2023) · Jordan Journal of Biological Sciences · doi:10.54319/jjbs/160404
A Genome-wide Association Study Identifies Novel Genetic Variants Associated with Neck or Shoulder Pain in the UK Biobank (N = 441,757)Preprint
Tao, Y., Pan, Q., Cai, T., Lu, Z. H., Haque, M., Dottorini, T., Colvin, L., Smith, B. H., & Meng, W. (2024) · medRxiv · doi:10.1101/2024.03.19.24304451
Additional file 1 of 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) · Figshare · doi:10.6084/m9.figshare.14450781
Author Response: Importance of Glutamine in Synaptic Vesicles Revealed by Functional Studies of SLC6A17 and Its Mutations Pathogenic for Intellectual Disability
Jia, X., Zhu, J., Bian, X., Liu, S., Yu, S., Liang, W., Jiang, L., Mao, R., & Rao, Y. (2023) · eLife · doi:10.7554/elife.86972.1.sa2
Neuronal protein phosphatase 1β regulates glutamate release, cortical myelination, node of Ranvier formation, and action potential propagation in the optic nervePreprint
McKee, C., Foley, K., Andersh, K. M., Marola, O. J., Wadzinski, B. E., Libby, R. T., Shrager, P. G., & Xia, H. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.10.593531
Research progress of the relationship between phosphoprotein phosphatases ( PPPs ) and neurodevelopmental disorders
Ji, W., Zheng, B., & Zhang, A. (2024) · Clinical Genetics · doi:10.1111/cge.14617
RAS Family Interactions: The SHOC2-MRAS-PP1 Complex in Noonan Syndrome
del Río, I. B., & Rodriguez‐Viciana, P. (2024) · Springer eBooks · doi:10.1007/978-3-031-62945-7_21
GATAD2B ‐related developmental and epileptic encephalopathy ( DEE ): Extending the epilepsy phenotype and a literature appraisal
Scorrano, G., Barcia, G., Champ, J., Courtin, T., Boddaert, N., Kamińska, A., Chémaly, N., & Nabbout, R. (2025) · Epilepsia Open · doi:10.1002/epi4.13133
Prenatal diagnosis of intellectual disability, autosomal dominant 29 with a nonsense pathogenic variant in SETBP1: a case report and literature review
Wei, Z., Yao, L., Zhang, L., Li, S., Xu, M., Wu, D., Li, W., & Chang, Y. (2025) · Frontiers in Genetics · doi:10.3389/fgene.2025.1463485
Contribution of families using the GenIDA database to the description of MED13L syndrome and literature review
Caumes, R., Burger, P., Mandel, J., Béhal, H., Ghoumid, J., & Smol, T. (2025) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-025-09618-4
Noonan-Like Syndrome with Loose Anagen Hair: Genetic and Phenotypic Variability, Differential Diagnosis
Volgina, S. Y., Kurbanova, Y. S., Abubakarov, A. S., Nimatulaev, A. M., Nikolaeva, E. A., & Gamirova, R. (2025) · Вопросы современной педиатрии · doi:10.15690/vsp.v24i3.2911
Ceramide transfer protein regulates G-protein coupled phospholipase signalling in Drosophila photoreceptorsPreprint
Mishra, S., Khan, A., Nath, V. R., Manoj, T., Thejaswini, B., Naik, A., Dasgupta, U., & Raghu, P. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.05.668821
AGO1 in neural progenitor cells orchestrates brain development and sociability via LIN28A-REELIN axisPreprint
Do, H., Kim, D., Jappelli, R., Yang, H., Jeon, Y.-S., Son, G., Ju, M., Son, J.-H., Ahn, I., Lim, C. K., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.01.679670
Case Report: Whole-exome sequencing revealed a de novo variant in SETBP1 gene in a Chinese family with developmental delay
Pan, J., Zhang, Y., Hou, J., Shi, N., Qu, H., Jiang, L., & Liu, H. (2025) · Frontiers in Genetics · doi:10.3389/fgene.2025.1637931
Systematic evaluation of de novo mutation calling tools using whole genome sequencing data
Shah, A., Monger, S., Troup, M., Ip, E., & Giannoulatou, E. (2025) · Briefings in Bioinformatics · doi:10.1093/bib/bbaf543
Complimentary vertebrate Wac models exhibit phenotypes relevant to DeSanto-Shinawi SyndromePreprint
Lee, K., Stafford, A. M., Pacheco-Vergara, M., Cichewicz, K., Canales, C. P., Seban, N., Corea, M., Rahbarian, D., Bonekamp, K. E., Gillie, G. R., et al. (2025) · eLife · doi:10.7554/elife.109104.1
Additional file 2 of Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders
Gillentine, M. A., Wang, T., Hoekzema, K., Rosenfeld, J., Liu, P., Guo, H., Kim, C. N., Vries, B. B. A. D., Vissers, L. E. L. M., Nordenskjöld, M., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14450784
Additional file 3 of Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders
Gillentine, M. A., Wang, T., Hoekzema, K., Rosenfeld, J., Liu, P., Guo, H., Kim, C. N., Vries, B. B. A. D., Vissers, L. E. L. M., Nordenskjöld, M., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14450793
Additional file 1 of Targeted next-generation sequencing identifies the disruption of the SHANK3 and RYR2 genes in a patient carrying a de novo t(1;22)(q43;q13.3) associated with signs of Phelan-McDermid syndrome
Bonaglia, M. C., Bertuzzo, S., Ciaschini, A. M., Discepoli, G., Castiglia, L., Romaniello, R., Zuffardi, O., & Fichera, M. (2020) · Figshare · doi:10.6084/m9.figshare.12470522
Additional file 2 of Identifying SETBP1 haploinsufficiency molecular pathways to improve patient diagnosis using induced pluripotent stem cells and neural disease modelling
Shaw, N. C., Chen, K., Farley, K. O., Hedges, M. G., Forbes, C., Baynam, G. S., Lassmann, T., & Fear, V. S. (2024) · UWA Profiles and Research Repository (UWA) · doi:10.6084/m9.figshare.27140535
Additional file 1 of Identifying SETBP1 haploinsufficiency molecular pathways to improve patient diagnosis using induced pluripotent stem cells and neural disease modelling
Shaw, N. C., Chen, K., Farley, K. O., Hedges, M. G., Forbes, C., Baynam, G. S., Lassmann, T., & Fear, V. S. (2024) · Figshare · doi:10.6084/m9.figshare.27140532
Additional file 3 of Identifying SETBP1 haploinsufficiency molecular pathways to improve patient diagnosis using induced pluripotent stem cells and neural disease modelling
Shaw, N. C., Chen, K., Farley, K. O., Hedges, M. G., Forbes, C., Baynam, G. S., Lassmann, T., & Fear, V. S. (2024) · Figshare · doi:10.6084/m9.figshare.27140538
Induced Pluripotent Stem Cell Line ICGi058-A Derived from Blood Mononuclear Cells of a Patient with Autism Spectrum Disorders and Multiple Chromosomal Rearrangements
Khabarova, A. A., Yan, A. P., & Minina, Y. M. (2025) · Russian Journal of Developmental Biology · doi:10.1134/s1062360425700250
Single-cell atlas of the fetal Down syndrome cortex uncovers chromosome 21 regulators of intellectual disability gene networksPreprint
Lattke, M., Tan, W. L., Sukumaran, S. K., Utami, K. H., Sintes, M., Sakthivel, S., Tan, J., Lim, A. T. J., Bansal, V. A., Rekopoulou, K., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.29.696602
Behavioral and epileptic phenotypes in a CHD2 ‐related developmental delay model
Mavashov, A., Turk, S., Sarusi, Y., Brusel, M., Perry, R. B., Quinn, S., Almog, Y., Vilian, K., Yam, M., Ulitsky, I., et al. (2025) · Epilepsia · doi:10.1002/epi.70073 · Cited by 2
Phenotypic Signatures of CTNNB1 Syndrome: Longitudinal Neuropsychological Outcomes and Three-Dimensional Facial MorphologyPreprint
Pallarès‐Sastre, M., Casado, A., Amayra, I., Anguiano, S., Escobar-Ramírez, B., Andreu-Montoriol, M., Roure-Ramis, O., Esteban, E. M., Sevillano, X., Heredia-Lidón, Á., et al. (2026) · medRxiv · doi:10.64898/2026.01.28.26344818
Neurocardiogenetics: Exploring the association of rare RYR2 variants with neuropsychiatric disorders in general and disease populations
Dababneh, S., Roberts, J. D., Tan, S., Wei, J., Wang, R., Estillore, J. P., Kallas, D., Tibbits, G. F., Sanatani, S., Chen, S. R. W., et al. (2026) · Journal of Neurogenetics · doi:10.1080/01677063.2026.2632080
Too rare to be random: genetic finding suggests previously unrecognized path of mutagenesisPreprint
Bohnlein, J., Maaß, J. G., Dennig, J., Burkart, S., Kaufmann, L. T., Brehm, M., Göbel, K., Kopp‐Schneider, A., Holland-Letz, T., Hinderhofer, K., et al. (2026) · medRxiv · doi:10.64898/2026.03.03.26346966

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