The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Recurrent 16p11.2 microdeletions in autism
Open accessAbstract
Autism is a childhood neurodevelopmental disorder with a strong genetic component, yet the identification of autism susceptibility loci remains elusive. We investigated 180 autism probands and 372 control subjects by array comparative genomic hybridization (aCGH) using a 19K whole-genome tiling path bacterial artificial chromosome microarray to identify submicroscopic chromosomal rearrangements specific to autism. We discovered a recurrent 16p11.2 microdeletion in two probands with autism and none in controls. The deletion spans approximately 500-kb and is flanked by approximately 147-kb segmental duplications (SDs) that are >99% identical, a common characteristic of genomic disorders. We assessed the frequency of this new autism genomic disorder by screening an additional 532 probands and 465 controls by quantitative PCR and identified two more patients but no controls with the microdeletion, indicating a combined frequency of 0.6% (4/712 autism versus 0/837 controls; Fisher exact test P = 0.044). We confirmed all 16p11.2 deletions using fluorescence in situ hybridization, microsatellite analyses and aCGH, and mapped the approximate deletion breakpoints to the edges of the flanking SDs using a custom-designed high-density oligonucleotide microarray. Bioinformatic analysis localized 12 of the 25 genes within the microdeletion to nodes in one interaction network. We performed phenotype analyses and found no striking features that distinguish patients with the 16p11.2 microdeletion as a distinct autism subtype. Our work reports the first frequency, breakpoint, bioinformatic and phenotypic analyses of a de novo 16p11.2 microdeletion that represents one of the most common recurrent genomic disorders associated with autism to date.
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“identical mutations may be associated with highly divergent phenotype”
From Autism risk factors: genes, environment, and gene-environment interactions (2012) · cites this paper as [40]
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In the citing paper
“recurrent structural variations involving one or a small number of genes, including: Neurexin 1 (NRXN1), Contactin 4 (CNTN4), Neuroligin 1 (NLGN1), Astrotactin 2 (ASTN2), and the contiguous genes Patched Domain Containing 1 (PTCHD1) and DEAD box Protein 53 (DDX53)”
From Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism (2011) · cites this paper as Kumar et al., 2008
Experimental — accuracy not yet measuredIn the citing paper
“Deletions and duplications of 16p11.2 have highly pleiotropic phenotypic effects, with strong links to ASD [8–19], ID [8, 10, 12, 14–16, 19–21], motor/developmental delay [8–10, 12, 13, 15–19, 22], dysmorphic features [8, 12, 16, 17, 22], and epilepsy/seizures [10, 12, 17].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [11]
In the citing paper
“Genetic screenings of ASD patients repeatedly identify 16p11.2 deletions & duplications, placing them among the strongest genetic risk factors for ASD [11, 13, 16, 38].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [11]
In the citing paper
“These include deletions and/or duplications at specific loci, including: 1q21.1, 15q11.2-13.1, 15q13.2-13.3, 16p11.2, 17q12, and 22q11.2”
From Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism (2011) · cites this paper as Kumar et al., 2008
In the citing paper
“identical CNVs have been associated with autism and schizophrenia, notably 16p11 rearrangements”
From Autism risk factors: genes, environment, and gene-environment interactions (2012) · cites this paper as [40]
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Citations
Cites
Lord, C., Rutter, M., & Le Couteur, A. (1994) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02172145 · Cited by 9,065
Lord, C., Risi, S., Lambrecht, L., Cook, E. H., Leventhal, B. L., DiLavore, P. C., Pickles, A., & Rutter, M. (2000) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1005592401947 · Cited by 7,520
Self-citationDetection of large-scale variation in the human genome
Iafrate, A. J., Feuk, L., Rivera, M. N., Listewnik, M. L., Donahoe, P. K., Qi, Y., Scherer, S. W., & Lee, C. (2004) · Nature Genetics · doi:10.1038/ng1416 · Cited by 2,892
Strong association of de novo copy number mutations with autism
Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J., et al. (2007) · Science · doi:10.1126/science.1138659 · Cited by 2,795
Self-citationLarge-scale copy number polymorphism in the human genome
Sebat, J., Lakshmi, B., Troge, J., Alexander, J., Young, J., Lundin, P., Månér, S., Massa, H., Walker, M., Chi, M., et al. (2004) · Science · doi:10.1126/science.1098918 · Cited by 2,557
Self-citationAutism as a strongly genetic disorder: evidence from a British twin study
Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E., & Rutter, M. (1995) · Psychological Medicine · doi:10.1017/s0033291700028099 · Cited by 2,461
Lord, C., Rutter, M., Goode, S., Heemsbergen, J., Jordan, H., Mawhood, L., & Schopler, E. (1989) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02211841 · Cited by 2,030
Autism spectrum disorders: developmental disconnection syndromes
Geschwind, D. H., & Levitt, P. (2007) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2007.01.009 · Cited by 1,411
Mapping autism risk loci using genetic linkage and chromosomal rearrangements
The Autism Genome Project Consortium (2007) · Nature Genetics · doi:10.1038/ng1985 · Cited by 1,402
Fine-scale structural variation of the human genome
Tüzün, E., Sharp, A. J., Bailey, J. A., Kaul, R., Morrison, V., Pertz, L. M., Haugen, E., Hayden, H. S., Albertson, D. G., Pinkel, D., et al. (2005) · Nature Genetics · doi:10.1038/ng1562 · Cited by 1,000
Segmental Duplications and Copy-Number Variation in the Human Genome
Sharp, A. J., Locke, D. P., McGrath, S. D., Cheng, Z., Bailey, J. A., Vallente, R. U., Pertz, L. M., Clark, R. A., Schwartz, S., Segraves, R., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/431652 · Cited by 983
A Twin Study of Autism in Denmark, Finland, Iceland, Norway and Sweden
Steffenburg, S., Gillberg, C., Hellgren, L., Andersson, L., Gillberg, I. C., Jakobsson, G., & Bohman, M. (1989) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.1989.tb00254.x · Cited by 780
The genetics of autistic disorders and its clinical relevance: a review of the literature
Freitag, C. M. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001896 · Cited by 638
Diagnostic genome profiling in mental retardation
de Vries, B. B. A., Pfundt, R., Leisink, M., Koolen, D. A., Vissers, L. E. L. M., Janssen, I. M., Reijmersdal, S. V., Nillesen, W. M., Huys, E. H. L. P. G., Leeuw, N. D., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/491719 · Cited by 605
A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism
Koolen, D. A., Vissers, L. E. L. M., Pfundt, R., de Leeuw, N., Knight, S. J. L., Regan, R., Kooy, R. F., Reyniers, E., Romano, C., Fichera, M., et al. (2006) · Nature Genetics · doi:10.1038/ng1853 · Cited by 465
Mazzucchelli, C., Vantaggiato, C., Ciamei, A., Fasano, S., Pakhotin, P., Krezel, W., Welzl, H., Wolfer, D. P., Pagès, G., Valverde, O., et al. (2002) · Neuron · doi:10.1016/s0896-6273(02)00716-x · Cited by 456
A positive autoregulatory loop of Jak-STAT signaling controls the onset of astrogliogenesis
He, F., Ge, W., Martinowich, K., Becker-Catania, S. G., Coskun, V., Zhu, W., Wu, H., Castro, D. S., Guillemot, F., Fan, G., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1440 · Cited by 413
The neuropoietic cytokine family in development, plasticity, disease and injury
Bauer, Š., Kerr, B. J., & Patterson, P. H. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2054 · Cited by 412
Vorstman, J. A. S., Staal, W. G., van Daalen, E., van Engeland, H., Hochstenbach, P. F. R., & Franke, L. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001757 · Cited by 353 · cited 1×
“Microscopically visible chromosomal rearrangements such as deletions and duplications have been identified in 1–3% of autism subjects (5).”
BackgroundThe 22q11.2 Deletion in Children
Vorstman, J. A. S., Morcus, M. E. J., Duijff, S. N., Klaassen, P., Boer, J. A. H., Beemer, F. A., Swaab, H., Kahn, R. S., & van Engeland, H. (2006) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/01.chi.0000228131.56956.c1 · Cited by 349
Oligonucleotide Microarray Analysis of Genomic Imbalance in Children with Mental Retardation
Friedman, J. M., Baross, Á., Delaney, A. D., Ally, A., Arbour, L. T., Asano, J. K., Bailey, D. K., Barber, S., Birch, P. H., Brown-John, M., et al. (2006) · The American Journal of Human Genetics · doi:10.1086/507471 · Cited by 330
Selzer, R. R., Richmond, T., Pofahl, N. J., Green, R. D., Eis, P. S., Nair, P., Brothman, A. R., & Stallings, R. L. (2005) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20243 · Cited by 263
Discovery of a previously unrecognized microdeletion syndrome of 16p11.2–p12.2
Ballif, B. C., Hornor, S. A., Jenkins, E., Madan‐Khetarpal, S., Surti, U., Jackson, K. E., Asamoah, A., Brock, P. L., Gowans, G. C., Conway, R. L., et al. (2007) · Nature Genetics · doi:10.1038/ng2107 · Cited by 248
Molecular genetics of autism spectrum disorder
Veenstra-VanderWeele, J. M., & Cook, E. H. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001505 · Cited by 224
Self-citationThe Serotonin 1a Receptor Gene Contains a TATA-less Promoter that Responds to MAZ and Sp1
Parks, C. L., & Shenk, T. E. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.8.4417 · Cited by 214
Molecular mechanisms of autism: a possible role for Ca2+ signaling
Krey, J. F., & Dolmetsch, R. E. (2007) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2007.01.010 · Cited by 169
Wagenstaller, J., Spranger, S., Lorenz‐Depiereux, B., Kazmierczak, B., Nathrath, M., Wahl, D., Heye, B., Gläser, D., Liebscher, V., Meitinger, T., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/521274 · Cited by 135
Fan, Y., Jayakar, P., Zhu, H., Barbouth, D., Sacharow, S. J., Morales, A., Carver, V. H., Benke, P. J., Mundy, P. C., & Elsas, L. J. (2007) · Human Mutation · doi:10.1002/humu.20581 · Cited by 128
Ghebranious, N., Giampietro, P. F., Wesbrook, F. P., & Rezkalla, S. H. (2007) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31837 · Cited by 121
Genome-wide aberrations in pancreatic adenocarcinoma
Nowak, N. J., Gaile, D. P., Conroy, J. M., McQuaid, D., Cowell, J. K., Carter, R. L., Goggins, M., Hruban, R. H., & Maitra, A. (2005) · Cancer Genetics and Cytogenetics · doi:10.1016/j.cancergencyto.2005.01.009 · Cited by 115
Self-citationGroffen, A. J. A., Friedrich, R., Brian, E. C., Ashery, U., & Verhage, M. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03755.x · Cited by 102
Miyazaki, T., Hashimoto, K., Uda, A., Sakagami, H., Nakamura, Y., Saito, S.-Y., Nishi, M., Kume, H., Tohgo, A., Kaneko, I., et al. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.06.043 · Cited by 83
Simon, T. J., Bish, J. P., Bearden, C. E., Ding, L., Ferrante, S., NGUYEN, V., Gee, J. C., McDonald‐McGinn, D. M., Zackai, E. H., & Emanuel, B. S. (2005) · Development and Psychopathology · doi:10.1017/s0954579405050364 · Cited by 78
Okamoto, S., Sherman, K., Bai, G., & Lipton, S. A. (2002) · Molecular Brain Research · doi:10.1016/s0169-328x(02)00440-0 · Cited by 76
Doc2α is an activity‐dependent modulator of excitatory synaptic transmission
Sakaguchi, G., Manabe, T., Kobayashi, K., Orita, S., Sasaki, T., Naito, A., Maeda, M. H., Igarashi, H., Katsuura, G., Nishioka, H., et al. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00855.x · Cited by 66
Autistic disorder and 22q11.2 duplication
Mukaddes, N. M., & Hergüner, S. (2006) · The World Journal of Biological Psychiatry · doi:10.1080/15622970601026701 · Cited by 66
Smith, K. M., Bauer, L., Fischer, M., Barkley, R. A., & NAVIA, B. A. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30127 · Cited by 34
Finelli, P., Natacci, F., Bonati, M. T., Gottardi, G., Engelen, J. J. M., de Die-Smulders, C. E. M., Sala, M., Giardino, D. L., & Larizza, L. (2004) · Journal of Medical Genetics · doi:10.1136/jmg.2003.016311 · Cited by 32
Cowell, J. K., Wang, Y. D., Head, K. L., Conroy, J. M., McQuaid, D., & Nowak, N. J. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6601588 · Cited by 31
Self-citationEngelen, J. J. M., de Die-Smulders, C. E. M., Dirckx, R., Verhoeven, W. M. A., Tuinier, S., Curfs, L., & Hamers, A. J. H. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10287 · Cited by 19
Genomic organization of TUPLEl/HIRA: a gene implicated in DiGeorge syndrome
Llevadot, R., Scambler, P. J., Estivill, X., et al. (1996) · Mammalian Genome · doi:10.1007/s003359900268 · Cited by 12
Characterization of the human PRIP-1 gene structure and transcriptional regulation
Murakami, A., Matsuda, M., Nakasima, A., et al. (2006) · Gene · doi:10.1016/j.gene.2006.07.005 · Cited by 8
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Metadata
- Authors
- Kumar, R. A., KaraMohamed, S., Sudi, J., Conrad, D. F., Brune, C., Badner, J. A., Gilliam, T. C., Nowak, N. J., Cook, E. H., Dobyns, W. B., & Christian, S. L.
- Affiliations
- University of Chicago (US)
- University of Illinois Chicago (US)
- Roswell Park Comprehensive Cancer Center (US)
- Corresponding author
- Christian, S. L.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-11-07
- Volume
- 17
- Issue
- 4
- Pages
- 628-638
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2162066558
- Cited by
- 731
- References
- 42
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 16 · 2023: 17 · 2022: 16 · 2021: 37 · 2020: 33 · 2019: 25 · 2018: 30 · 2017: 32 · 2016: 21 · 2015: 41 · 2014: 42 · 2013: 46 · 2012: 57
- FWCI
- 35.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Human Molecular Genetics (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Autism Speaks
- National Institutes of Health
- National Institute of Mental Health (MH 64547, 1R01MH64547-01, R01MH064547)
- National Institute of Neurological Disorders and Stroke (R01NS051812, 1R01 NS51812)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- autism spectrum disorder, 16p11.2 microdeletion, genomic disorders, segmental duplication, de novo deletion, chromosomal rearrangements, gene interaction networks, autism subtypes
- MeSH terms
- Autistic Disorder, Base Sequence, Child, Chromosome Deletion, Chromosomes, Human, Pair 16, Female, Gene Frequency, Humans, Male, Pedigree, Phenotype, Case-Control Studies, Polymerase Chain Reaction, In Situ Hybridization, Fluorescence, DNA Primers, Microsatellite Repeats, Chromosome Breakage, Genetic Predisposition to Disease, Chromosomes, Artificial, Bacterial
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