Disentangling the heterogeneity of autism spectrum disorder through genetic findings
Open accessAbstract
Autism spectrum disorder (ASD) represents a heterogeneous group of disorders, which presents a substantial challenge to diagnosis and treatment. Over the past decade, considerable progress has been made in the identification of genetic risk factors for ASD that define specific mechanisms and pathways underlying the associated behavioural deficits. In this Review, we discuss how some of the latest advances in the genetics of ASD have facilitated parsing of the phenotypic heterogeneity of this disorder. We argue that only through such advances will we begin to define endophenotypes that can benefit from targeted, hypothesis-driven treatments. We review the latest technologies used to identify and characterize the genetics underlying ASD and then consider three themes-single-gene disorders, the gender bias in ASD, and the genetics of neurological comorbidities-that highlight ways in which we can use genetics to define the many phenotypes within the autism spectrum. We also present current clinical guidelines for genetic testing in ASD and their implications for prognosis and treatment.
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ASD is by now considered as a multifactorial disease.
“For this reason, ASD is by now considered as a multifactorial disease [95,96,97].”
From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [95]
Schizophrenia, ADHD, Autism, and potentially other DSM-defined disorders each constitute a highly heterogeneous set of etiologies.
“The first challenge is the ever-expanding evidence that Schizophrenia (Meda et al., 2014; Satterthwaite and Baker, 2015), ADHD (Costa Dias et al., 2015; Fair et al., 2012a; Gates et al., 2014; Karalunas et al., 2014), Autism (Jeste and Geschwind, 2014; Rudie et al., 2012), and potentially other DSM defined disorders, each constitutes a highly heterogeneous set of etiologies.”
From Development of large-scale functional networks from birth to adulthood: A guide to the neuroimaging literature (2017) · cites this paper as Jeste and Geschwind, 2014
A likely reason why a unifying microbial composition is unlikely to be found is the large heterogeneity of ASD phenotypes.
“A likely reason, however, why a unifying microbial composition is unlikely to be found is due to the large heterogeneity of ASD phenotypes [81].”
From Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders (2018) · cites this paper as [81]
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Cites
Diagnostic and Statistical Manual of Mental Disorders
American Psychiatric Association (2013) · doi:10.1176/appi.books.9780890425596 · Cited by 116,369 · see citing works
Christakis, D., Richards, J. A., Zimmerman, F. J., Garrison, M. M., Xu, D., & Yapanel, U. H. (2009) · Cited by 2,290 · see citing works
The causes and consequences of genetic heterogeneity in cancer evolution
Burrell, R. A., McGranahan, N., Bartek, J., & Swanton, C. (2013) · Nature · doi:10.1038/nature12625 · Cited by 2,262 · see citing works
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× · see citing works
“8,9,13 Exome or genome sequencing moves genetic analysis of patients to the level of the single base pair, expanding testing beyond individual or small groups of related genes, such as those usually detected by CMA.”
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 · see citing works
Self-citationEpidemiology of Pervasive Developmental Disorders
Fombonne, E. (2009) · Pediatric Research · doi:10.1203/pdr.0b013e31819e7203 · Cited by 1,971 · see citing works
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 · see citing works
Recurrence Risk for Autism Spectrum Disorders: A Baby Siblings Research Consortium Study
Ozonoff, S., Young, G. S., Carter, A., Messinger, D., Yirmiya, N., Zwaigenbaum, L., Bryson, S., Carver, L. J., Constantino, J. N., Dobkins, K., et al. (2011) · Pediatrics · doi:10.1542/peds.2010-2825 · Cited by 1,429 · see citing works
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 · see citing works
Self-citationMotor coordination in autism spectrum disorders: A synthesis and meta-analysis
Fournier, K. A., Hass, C. J., Naik, S. K., Lodha, N., & Cauraugh, J. H. (2010) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-010-0981-3 · Cited by 1,271 · see citing works
Sirolimus for Angiomyolipoma in Tuberous Sclerosis Complex or Lymphangioleiomyomatosis
Bissler, J. J., McCormack, F. X., Young, L. R., Elwing, J., Chuck, G., Leonard, J. M., Schmithorst, V. J., Laor, T., Brody, A. S., Bean, J. A., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa063564 · Cited by 1,250 · see citing works
The TSC1–TSC2 complex: a molecular switchboard controlling cell growth
Huang, J., & Manning, B. D. (2008) · Biochemical Journal · doi:10.1042/bj20080281 · Cited by 1,237 · see citing works
Curatolo, P., Bombardieri, R., & Jóźwiak, S. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61279-9 · Cited by 1,106 · see citing works
Practice parameter: Screening and diagnosis of autism
Filipek, P. A., Accardo, P., Ashwal, S., Baranek, G. T., Cook, E. H., Dawson, G., Gordon, B., Gravel, J. S., Johnson, C. P., Kallen, R. J., et al. (2000) · Neurology · doi:10.1212/wnl.55.4.468 · Cited by 1,061 · see citing works
Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice
Tsai, P. T., Hull, C., Chu, Y., Greene-Colozzi, E., Sadowski, A. R., Leech, J. M., Steinberg, J., Crawley, J. N., Regehr, W. G., & Sahin, M. (2012) · Nature · doi:10.1038/nature11310 · Cited by 888 · see citing works
Bissler, J. J., Kingswood, J. C., Radzikowska, E., Zonnenberg, B. A., Frost, M., Белоусова, Е. Д., Sauter, M., Nonomura, N., Brakemeier, S., de Vries, P. J., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(12)61767-x · Cited by 880 · see citing works
Reversal of learning deficits in a Tsc2+/− mouse model of tuberous sclerosis
Ehninger, D., Han, S., Shilyansky, C., Zhou, Y., Li, W., Kwiatkowski, D. J., Ramesh, V., & Silva, A. J. (2008) · Nature Medicine · doi:10.1038/nm1788 · Cited by 879 · see citing works
CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics
Malhotra, D., & Sebat, J. (2012) · Cell · doi:10.1016/j.cell.2012.02.039 · Cited by 854 · see citing works
Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene
Alarcón, M., Abrahams, B. S., Stone, J. L., Duvall, J. A., Perederiy, J. V., Bomar, J. M., Sebat, J., Wigler, M., Martin, C. L., Ledbetter, D. H., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.09.005 · Cited by 818 · see citing works
Self-citationImpairment in movement skills of children with autistic spectrum disorders
Green, D., Charman, T., Pickles, A. R., Chandler, S., Loucas, T., Simonoff, E. A., & Baird, G. (2009) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2008.03242.x · Cited by 742 · see citing works
A behavioral comparison of male and female adults with high functioning autism spectrum conditions
Lai, M.-C., Lombardo, M. V., Pasco, G., Ruigrok, A. N. V., Wheelwright, S. J., Sadek, S. A., Chakrabarti, B., MRC AIMS Consortium, & Baron-Cohen, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020835 · Cited by 650 · see citing works
Dworzynski, K., Ronald, A., Bolton, P., & Happé, F. (2012) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2012.05.018 · Cited by 633 · cited 1× · see citing works
“55 Additionally, females with ASD tend to show greater cog nitive impairment, with the male:female ratio being close to 1:1 in severely intellectually disabled populations.”
Arking, D. E., Cutler, D. J., Brune, C. W., Teslovich, T. M., West, K., Ikeda, M., Rea, A., Guy, M., Lin, S., Cook, E. H., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.09.015 · Cited by 590 · see citing works
Krakowiak, P., Goodlin‐Jones, B. L., Hertz‐Picciotto, I., Croen, L., & Hansen, R. L. (2008) · Journal of Sleep Research · doi:10.1111/j.1365-2869.2008.00650.x · Cited by 589 · see citing works
Patterns of growth in verbal abilities among children with autism spectrum disorder.
Anderson, D. K., Lord, C., Risi, S., DiLavore, P. S., Shulman, C., Thurm, A., Welch, K., & Pickles, A. (2007) · Journal of Consulting and Clinical Psychology · doi:10.1037/0022-006x.75.4.594 · Cited by 553 · see citing works
Schaefer, G. B., & Mendelsohn, N. J. (2013) · Genetics in Medicine · doi:10.1038/gim.2013.32 · Cited by 537 · see citing works
Examining and interpreting the female protective effect against autistic behavior
Robinson, E. B., Lichtenstein, P., Anckarsäter, H., Happé, F., & Ronald, A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211070110 · Cited by 531 · see citing works
Smalley, S. L., Tanguay, P. E., Smith, M., & Gutierrez, G. (1992) · Journal of Autism and Developmental Disorders · doi:10.1007/bf01048239 · Cited by 518 · see citing works
Dyspraxia in autism: association with motor, social, and communicative deficits
Dziuk, M., Larson, J. C. G., Apostu, A., Mahone, E. M., DENCKLA, M. B., & Mostofsky, S. H. (2007) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2007.00734.x · Cited by 466 · see citing works
Meikle, L., Talos, D. M., Onda, H., Pollizzi, K., Rotenberg, A., Sahin, M., Jensen, F. E., & Kwiatkowski, D. J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5540-06.2007 · Cited by 462 · see citing works
Using Whole-Exome Sequencing to Identify Inherited Causes of Autism
Yu, T. W., Chahrour, M. H., Coulter, M. E., Jiralerspong, S., Okamura-Ikeda, K., Ataman, B., Schmitz-Abe, K., Harmin, D. A., Adli, M., Malik, A. N., et al. (2013) · Neuron · doi:10.1016/j.neuron.2012.11.002 · Cited by 442 · see citing works
The role of epilepsy and epileptiform EEGs in autism spectrum disorders
Spence, S. J., & Schneider, M. T. (2009) · Pediatric Research · doi:10.1203/pdr.0b013e31819e7168 · Cited by 418 · see citing works
A pilot open label, single dose trial of fenobam in adults with fragile X syndrome
Berry-Kravis, E., Hessl, D., Coffey, S., Hervey, C., Schneider, A., Yuhas, J., Hutchison, J., Snape, M., Tranfaglia, M., Nguyen, D. V., et al. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2008.063701 · Cited by 411 · see citing works
Sex differences in the evaluation and diagnosis of autism spectrum disorders among children
Giarelli, E., Wiggins, L. D., Rice, C. E., Levy, S. E., Kirby, R. S., Pinto-Martin, J., & Mandell, D. (2010) · Disability and Health Journal · doi:10.1016/j.dhjo.2009.07.001 · Cited by 398 · see citing works
Smalley, S. L. (1988) · Archives of General Psychiatry · doi:10.1001/archpsyc.1988.01800340081013 · Cited by 349 · see citing works
Berry-Kravis, E. M., Hessl, D., Rathmell, B., Zarevics, P., Cherubini, M., Walton-Bowen, K., Mu, Y., Nguyen, D. V., Gonzalez-Heydrich, J., Wang, P. P., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004214 · Cited by 328 · see citing works
Autism Symptoms and Internalizing Psychopathology in Girls and Boys with Autism Spectrum Disorders
Solomon, M., Miller, M., Taylor, S. L., Hinshaw, S. P., & Carter, C. S. (2012) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-011-1215-z · Cited by 326 · see citing works
SHANK1 Deletions in Males with Autism Spectrum Disorder
Sato, D., Lionel, A. C., Leblond, C. S., Prasad, A., Pinto, D., Walker, S., O'Connor, I., Russell, C., Drmic, I. E., Hamdan, F. F., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.03.017 · Cited by 318 · see citing works
Jóźwiak, S., Kotulska, K., Domańska‐Pakieła, D., Łojszczyk, B., Syczewska, M., Chmielewski, D., Dunin-Wąsowicz, D., Kmieć, T., Szymkiewicz–Dangel, J., Borszewska-Kornacka, M. K., et al. (2011) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2011.03.010 · Cited by 310 · see citing works
Neuro‐epileptic determinants of autism spectrum disorders in tuberous sclerosis complex
Bolton, P., Park, R. J., Higgins, N. J., Griffiths, P. D., & Pickles, A. R. (2002) · Brain · doi:10.1093/brain/awf124 · Cited by 300 · see citing works
Wiggs, L. D., & Stores, G. (1996) · Journal of Intellectual Disability Research · doi:10.1046/j.1365-2788.1996.799799.x · Cited by 279 · see citing works
Malow, B. A., Byars, K. C., Johnson, K., Weiss, S. K., Bernal, P., Goldman, S. E., Panzer, R., Coury, D. L., & Glaze, D. G. (2012) · PEDIATRICS · doi:10.1542/peds.2012-0900i · Cited by 277 · see citing works
Tuberous sclerosis complex proteins control axon formationPreprint
Choi, Y.-J., Nardo, A. D., Kramvis, I., Meikle, L. M., Kwiatkowski, D. J., Şahin, M., & He, X. (2008) · Genes & Development · doi:10.1101/gad.1685008 · Cited by 258 · see citing works
Scott-Van Zeeland, A. A., Abrahams, B. S., Alvarez-Retuerto, A. I., Sonnenblick, L. I., Rudie, J. D., Ghahremani, D., Mumford, J. A., Poldrack, R. A., Dapretto, M., Geschwind, D. H., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3001344 · Cited by 252 · see citing works
Self-citationAssociation of tuberous sclerosis of temporal lobes with autism and atypical autism
Bolton, P., & Griffiths, P. D. (1997) · The Lancet · doi:10.1016/s0140-6736(97)80012-8 · Cited by 250 · see citing works
Cognitive deficits in Tsc1+/−mice in the absence of cerebral lesions and seizures
Goorden, S. M. I., van Woerden, G. M., van der Weerd, L., Cheadle, J. P., & Elgersma, Y. (2007) · Annals of Neurology · doi:10.1002/ana.21317 · Cited by 247 · see citing works
Tsc2-Rheb signaling regulates EphA-mediated axon guidance
Nie, D. A., Nardo, A. D., Han, J. M., Baharanyi, H., Kramvis, I., Huynh, T., Dabora, S. L., Codeluppi, S., Pandolfi, P. P., Pasquale, E. B., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2477 · Cited by 243 · see citing works
Clinical characteristics of children with autism spectrum disorder and co-occurring epilepsy.
Viscidi, E. W., Triche, E. W., Pescosolido, M. F., McLean, R. L., Joseph, R. M., Spence, S. J., & Morrow, E. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067797 · Cited by 235 · see citing works
Open-label add-on treatment trial of minocycline in fragile X syndrome.
Paribello, C., Tao, L., Folino, A., Berry-Kravis, E., Tranfaglia, M., Ethell, I. M., & Ethell, D. W. (2010) · BMC Neurology · doi:10.1186/1471-2377-10-91 · Cited by 223 · see citing works
Open-Label Treatment Trial of Lithium to Target the Underlying Defect in Fragile X Syndrome
Berry-Kravis, E., Sumis, A., Hervey, C., Nelson, M., Porges, S. W., Weng, N., Weiler, I. J., & Greenough, W. T. (2008) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0b013e31817dc447 · Cited by 215 · see citing works
Wiznitzer, M. (2004) · Journal of Child Neurology · doi:10.1177/08830738040190090701 · Cited by 214 · see citing works
Motor impairment in sibling pairs concordant and discordant for autism spectrum disorders
Hilton, C. L., Zhang, Y., Whilte, M. R., Klohr, C. L., & Constantino, J. N. (2011) · Autism · doi:10.1177/1362361311423018 · Cited by 211 · see citing works
Genome-wide analyses of human perisylvian cerebral cortical patterning
Abrahams, B. S., Tentler, D., Perederiy, J. V., Oldham, M. C., Coppola, G., & Geschwind, D. H. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706128104 · Cited by 198 · see citing works
Self-citationCharacterization of Autism in Young Children With Tuberous Sclerosis Complex
Jeste, S., Şahin, M., Bolton, P., Ploubidis, G. B., & Humphrey, A. (2007) · Journal of Child Neurology · doi:10.1177/0883073807309788 · Cited by 195 · see citing works
Self-citationAutism genetics: searching for specificity and convergence
Berg, J. M., & Geschwind, D. H. (2012) · Genome Biology · doi:10.1186/gb-2012-13-7-247 · Cited by 192 · see citing works
Self-citationWhat does CNTNAP2 reveal about autism spectrum disorder?
Peñagarikano, O., & Geschwind, D. H. (2012) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2012.01.003 · Cited by 191 · see citing works
Self-citationSex differences in repetitive stereotyped behaviors in autism: Implications for genetic liability
Szatmari, P., Liu, X., Goldberg, J., Zwaigenbaum, L., Paterson, A. D., Woodbury‐Smith, M., Georgiades, S., Duku, E., & Thompson, A. (2012) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31238 · Cited by 187 · cited 1× · see citing works
“51 A related conten tion supporting the FPE is that in the setting of compar able genetic risk, males are more likely to meet clinical criteria for ASD than are females.”
Wiggs, L. D., & Stores, G. (1996) · Journal of Intellectual Disability Research · doi:10.1111/j.1365-2788.1996.tb00662.x · Cited by 186 · see citing works
Zwaigenbaum, L., Bryson, S. E., Szatmari, P., Brian, J., Smith, I. M., Roberts, W., Vaillancourt, T., & Roncadin, C. (2012) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-012-1515-y · Cited by 178 · see citing works
Genetics evaluation for the etiologic diagnosis of autism spectrum disorders
Schaefer, G. B., & Mendelsohn, N. J. (2008) · Genetics in Medicine · doi:10.1097/gim.0b013e31815efdd7 · Cited by 173 · see citing works
Hus, V., Pickles, A., Cook, E. H., Risi, S., & Lord, C. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.08.044 · Cited by 172 · see citing works
Bölte, S., Duketis, E., Poustka, F., & Holtmann, M. (2011) · Autism · doi:10.1177/1362361310391116 · Cited by 168 · see citing works
Urraca, N., Cleary, J., Brewer, V., Pivnick, E. K., McVicar, K., Thibert, R. L., Schanen, N. C., Esmer, C., Lamport, D., & Reiter, L. T. (2013) · Autism Research · doi:10.1002/aur.1284 · Cited by 164 · see citing works
NEUROPSYCHOLOGICAL ASPECTS OF TUBEROUS SCLEROSIS IN RELATION TO EPILEPSY AND MRI FINDINGS
Jambaqué, I., Cusmai, R., Curatolo, P., Cortesi, F., Perrot, C. Y., & Dulac, O. (1991) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.1991.tb14947.x · Cited by 163 · see citing works
Epilepsy and autism spectrum disorders: are there common developmental mechanisms?
Brooks-Kayal, A. (2010) · Brain and Development · doi:10.1016/j.braindev.2010.04.010 · Cited by 162 · see citing works
Understanding sex bias in autism spectrum disorder
Werling, D. M., & Geschwind, D. H. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1301602110 · Cited by 135 · see citing works
Self-citationThe neurology of autism spectrum disorders
Jeste, S. (2011) · Current Opinion in Neurology · doi:10.1097/wco.0b013e3283446450 · Cited by 128 · see citing works
Self-citationHattier, M. A., Matson, J. L., Tureck, K., & Horovitz, M. (2011) · Research in Developmental Disabilities · doi:10.1016/j.ridd.2011.07.028 · Cited by 104 · see citing works
Autism and the Cerebellum: Evidence from Tuberous Sclerosis
Weber, A. M., Egelhoff, J. C., McKellop, J. M., & Franz, D. N. (2000) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1005679108529 · Cited by 100 · see citing works
Cerebellar Lesions in Tuberous Sclerosis Complex: Neurobehavioral and Neuroimaging Correlates
Eluvathingal, T. J., Behen, M. E., Chugani, H. T., Janisse, J., Bernardi, B., Chakraborty, P., Juhasz, C., Muzik, O., & Chugani, D. C. (2006) · Journal of Child Neurology · doi:10.1177/08830738060210100301 · Cited by 100 · see citing works
Pop, A. S., Gomez‐Mancilla, B., Neri, G., Willemsen, R., & Gasparini, F. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3330-3 · Cited by 96 · see citing works
Gender Bias, Female Resilience, and the Sex Ratio in Autism
Constantino, J. N., & Charman, T. (2012) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2012.05.017 · Cited by 92 · see citing works
Annotation: Tuberous Sclerosis
Harrison, J., & Bolton, P. (1997) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.1997.tb01687.x · Cited by 86 · see citing works
Rare inherited variation in autism: Beginning to see the forest and a few trees
Stein, J. L., Parikshak, N. N., & Geschwind, D. H. (2013) · Neuron · doi:10.1016/j.neuron.2013.01.010 · Cited by 68 · see citing works
Self-citationTargeted treatment trials for tuberous sclerosis and autism: no longer a dream
Şahin, M. (2012) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2012.04.008 · Cited by 66 · see citing works
Increased Brain Apparent Diffusion Coefficient in Tuberous Sclerosis
Garaci, F. G., Floris, R., Bozzao, A., Manenti, G., Simonetti, A., Lupattelli, T., Curatolo, P., & Simonetti, G. (2004) · Radiology · doi:10.1148/radiol.2322030198 · Cited by 66 · see citing works
Pragmatic language and school related linguistic abilities in siblings of children with autism
Ben-Yizhak, N., Yirmiya, N., Seidman, I., Alon, R., Lord, C., & Sigman, M. (2011) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-010-1096-6 · Cited by 62 · see citing works
Diffusion Features of White Matter in Tuberous Sclerosis With Tractography
Krishnan, M. L., Commowick, O., Jeste, S., Weisenfeld, N., Hans, A., Gregas, M. C., Şahin, M., & Warfield, S. K. (2010) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2009.08.001 · Cited by 62 · see citing works
Self-citationThe Genetics of Autism Spectrum Disorders – A Guide for Clinicians
Heil, K. M., & Schaaf, C. P. (2012) · Current Psychiatry Reports · doi:10.1007/s11920-012-0334-3 · Cited by 62 · see citing works
Widjaja, E., Simão, G. N., Mahmoodabadi, S. Z., Ochi, A., Snead, O. C., Rutka, J. T., & Otsubo, H. (2010) · Epilepsy Research · doi:10.1016/j.eplepsyres.2010.01.008 · Cited by 47 · see citing works
Royall, D. (2014) · Canadian Journal of Dietetic Practice and Research · doi:10.3148/75.2.2014.56 · Cited by 41 · see citing works
The effects of seizures on the connectivity and circuitry of the developing brain
Swann, J. W. (2004) · Mental Retardation and Developmental Disabilities Research Reviews · doi:10.1002/mrdd.20018 · Cited by 39 · see citing works
Davidson, J., & Orsini, M. (2013) · University of Minnesota Press eBooks · doi:10.5749/minnesota/9780816688883.003.0006 · Cited by 33 · see citing works
Cerebral diffusion tensor images in children with tuberous sclerosis: a preliminary report
Lee, W., Wang, Y. H., Huang, K.-M., & Peng, S. S. (2004) · Pediatric Radiology · doi:10.1007/s00247-004-1162-3 · Cited by 32 · see citing works
An evaluation of the role and treatment of elevated male hormones in autism spectrum disorders
Geier, D. A., Kern, J. K., King, P. G., Sykes, L. K., & Geier, M. R. (2012) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-2012-1876 · Cited by 30 · see citing works
van Rijn, S., Bierman, M., Bruining, H., & Swaab, H. (2012) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.06.004 · Cited by 23 · see citing works
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Belgard, T. G., Janković, I., Lowe, J. K., & Geschwind, D. H. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.34 · Cited by 14 · see citing works
Self-citationDonnelly, S. L., Wolpert, C. M., Menold, M. M., Bass, M. P., Gilbert, J. R., Cuccaro, M. L., Delong, G. R., & Pericak-Vance, M. A. (2000) · American Journal of Medical Genetics · doi:10.1002/1096-8628(20000612)96:3
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Grayson, D. S., & Fair, D. A. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.01.079 · Cited by 411 · see citing works
“DSG was supported by an Autism Speaks Dennis Weatherstone Predoctoral Fellowship (#9591).”
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Self-citationCotney, J., Muhle, R. A., Sanders, S. J., Liu, L., Willsey, A. J., Niu, W., Liu, W., Klei, L., Lei, J., Yin, J., et al. (2015) · Nature Communications · doi:10.1038/ncomms7404 · Cited by 350 · see citing works
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Constantino, J. N., & Charman, T. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(15)00151-9 · Cited by 294 · see citing works
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Chen, C. P., Keown, C. L., Jahedi, A., Nair, A., Pflieger, M. E., Bailey, B. A., & Müller, R.-A. (2015) · NeuroImage: Clinical · doi:10.1016/j.nicl.2015.04.002 · Cited by 183 · see citing works
Quesnel-Vallières, M., Dargaei, Z., Irimia, M., Gonatopoulos-Pournatzis, T., Ip, J. Y., Wu, M., Sterne-Weiler, T., Nakagawa, S., Woodin, M. A., Blencowe, B. J., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.11.033 · Cited by 178 · see citing works
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Veenstra-VanderWeele, J., Cook, E. H., King, B. H., Zarevics, P., Cherubini, M., Walton-Bowen, K., Bear, M. F., Wang, P. P., & Carpenter, R. L. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.237 · Cited by 168 · see citing works
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Wilson, R. B., Vangala, S., Elashoff, D., Safari, T., & Smith, B. A. (2021) · Sensors · doi:10.3390/s21020616 · Cited by 59 · see citing works
Walsh, J. J., Llorach, P., Cardozo Pinto, D. F., Wenderski, W., Christoffel, D. J., Salgado, J. S., Heifets, B. D., Crabtree, G. R., & Malenka, R. C. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-01091-6 · Cited by 56 · see citing works
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Segatto, M., Tonini, C., Pfrieger, F. W., Trezza, V., & Pallottini, V. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133317 · Cited by 51 · see citing works
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Burrows, C. A., Timpano, K. R., & Uddin, L. Q. (2017) · Clinical Psychological Science · doi:10.1177/2167702616683506 · Cited by 43 · see citing works
Oh, H., Lee, S., Oh, Y., Kim, S., Kim, Y. S., Yang, Y., Choi, W., Yoo, Y.-E., Cho, H., Lee, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39203-z · Cited by 32 · see citing works
Southon, C. (2022) · Frontiers in Psychology · doi:10.3389/fpsyg.2022.958013 · Cited by 33 · see citing works
Muratori, F., Turi, M., Prosperi, M., Narzisi, A., Valeri, G., Guerrera, S., Santocchi, E., Apicella, F., Lattarulo, C., Calderoni, S., et al. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00107 · Cited by 29 · see citing works
Yang, M., Lewis, F., Foley, G., & Crawley, J. N. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.04.023 · Cited by 28 · see citing works
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- Authors
- Jeste, S. S., & Geschwind, D. H.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Jeste, Shafali S.
- Venue
- Nature Reviews Neurology
- Published
- 2014-01-28
- Volume
- 10
- Issue
- 2
- Pages
- 74-81
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- PMC
- PMC4125617
- OpenAlex
- W1984331840
- Cited by
- 644
- References
- 90
- Citations by year
- 2026: 24 · 2025: 28 · 2024: 45 · 2023: 57 · 2022: 39 · 2021: 51 · 2020: 90 · 2019: 61 · 2018: 45 · 2017: 44 · 2016: 69 · 2015: 69 · 2014: 21 · 2013: 1
- FWCI
- 6.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (5r01mh094714-04)
- National Institute of Mental Health (R01-MH094714, K23MH094517)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Keywords
- autism spectrum disorder, genetic heterogeneity, monogenic disorders, neurological comorbidity, endophenotypes, genetic risk factors, genetic testing guidelines, etiology, neurodevelopmental disorders
- MeSH terms
- Animals, Brain, Child Development Disorders, Pervasive, Genetic Testing, Humans, Mutation, Genetic Predisposition to Disease, Methyl-CpG-Binding Protein 2
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.
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