Genetics and genomics of autism spectrum disorder: Embracing complexity

Human Molecular Genetics

Volumn 24, Issue R1, 2015, Pages R24-R31

  De Rubeis, Silvia ^a   Buxbaum, Joseph D ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AUTISM; CHILD PSYCHIATRY; CLINICAL OBSERVATION; GENETIC ASSOCIATION; GENETIC HETEROGENEITY; GENETIC RISK; GENETIC SUSCEPTIBILITY; GENOMICS; GENOTYPE PHENOTYPE CORRELATION; HUMAN; MEDICAL GENETICS; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REVIEW; ANIMAL; GENETIC ASSOCIATION STUDY; GENETIC VARIATION; GENETICS; INHERITANCE; RISK FACTOR;

ANIMALS; AUTISM SPECTRUM DISORDER; GENETIC ASSOCIATION STUDIES; GENETIC VARIATION; GENOMICS; HUMANS; INHERITANCE PATTERNS; RISK FACTORS;

EID: 84943799823     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddv273     Document Type: Review

References (106)

1. Szatmari, P., Georgiades, S., Duku, E., Bennett, T.A., Bryson, S., Fombonne, E., Mirenda, P., Roberts, W., Smith, I.M., Vaillancourt, T. et al. (2015) Developmental trajectories of symptom severity and adaptive functioning in an inception cohort of preschool children with autism spectrumdisorder. JAMA Psychiatry, 72, 276-283.
2. Paul, R., Loomis, R. and Chawarska, K. (2014) Adaptive behavior in toddlers under two with autism spectrum disorders. J. Autism Dev. Disord., 44, 264-270.
3. Vivanti, G., Barbaro, J., Hudry, K., Dissanayake, C. and Prior, M. (2013) Intellectual development in autism spectrum disorders: new insights from longitudinal studies. Front. Hum. Neurosci., 7, 354.
4. Magiati, I., Tay, X.W. and Howlin, P. (2014) Cognitive, language, social and behavioural outcomes in adults with autism spectrumdisorders: a systematic review of longitudinal follow-up studies in adulthood. Clin. Psychol. Rev., 34, 73-86.
5. Tager-Flusberg, H. and Kasari, C. (2013) Minimally verbal school-aged children with autism spectrum disorder: the neglected end of the spectrum. Autism Res., 6, 468-478.
6. Aldinger, K.A., Lane, C.J., Veenstra-VanderWeele, J. and Levitt, P. (2015) Patterns of risk for multiple co-occurring medical conditions replicate across distinct cohorts of children with autism spectrum disorder. Autism Res., doi: 10.1002/aur.1492.
7. Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E. and Rutter, M. (1995) Autism as a strongly genetic disorder: evidence from a British twin study. Psychol. Med., 25, 63-77.
8. Ritvo, E.R., Freeman, B.J., Mason-Brothers, A., Mo, A. and Ritvo, A.M. (1985) Concordance for the syndrome of autism in 40 pairs of afflicted twins. Am. J. Psychiatry, 142, 74-77.
9. Steffenburg, S., Gillberg, C., Hellgren, L., Andersson, L., Gillberg, I.C., Jakobsson, G. and Bohman, M. (1989) A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J. Child Psychol. Psychiatry, 30, 405-416.
10. Folstein, S. and Rutter, M. (1977) Infantile autism: a genetic study of 21 twin pairs. J. Child Psychol. Psychiatry, 18, 297-321.
11. Gaugler, T., Klei, L., Sanders, S.J., Bodea, C.A., Goldberg, A.P., Lee, A.B., Mahajan, M., Manaa, D., Pawitan, Y., Reichert, J. et al. (2014) Most genetic risk for autism resides with common variation. Nat. Genet., 46, 881-885.
12. Klei, L., Sanders, S.J., Murtha, M.T., Hus, V., Lowe, J.K., Willsey, A.J., Moreno-De-Luca, D., Yu, T.W., Fombonne, E., Geschwind, D. et al. (2012) Common genetic variants, acting additively, are a major source of risk for autism. Mol. Autism, 3, 9.
13. Sandin, S., Lichtenstein, P., Kuja-Halkola, R., Larsson, H., Hultman, C.M. and Reichenberg, A. (2014) The familial risk of autism. JAMA, 311, 1770-1777.
14. Devlin, B. and Scherer, S.W. (2012) Genetic architecture in autism spectrum disorder. Curr. Opin. Genet. Dev., 22, 229-237.
15. Betancur, C. (2011) Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting. Brain Res., 1380, 42-77.
16. Anney, R., Klei, L., Pinto, D., Almeida, J., Bacchelli, E., Baird, G., Bolshakova, N., Bolte, S., Bolton, P.F., Bourgeron, T. et al. (2012) Individual common variants exert weak effects on the risk for autism spectrum disorders. Hum. Mol. Genet., 21, 4781-4792.
17. Wang, K., Zhang, H., Ma, D., Bucan, M., Glessner, J.T., Abrahams, B.S., Salyakina, D., Imielinski, M., Bradfield, J.P., Sleiman, P.M. et al. (2009) Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature, 459, 528-533.
18. Ma, D., Salyakina, D., Jaworski, J.M., Konidari, I., Whitehead, P.L., Andersen, A.N., Hoffman, J.D., Slifer, S.H., Hedges, D.J., Cukier, H.N. et al. (2009) A genome-wide association study of autism reveals a common novel risk locus at 5p14.1. Ann. Hum. Genet., 73, 263-273.
19. Weiss, L.A., Arking, D.E., Daly, M.J. and Chakravarti, A. (2009) A genome-wide linkage and association scan reveals novel loci for autism. Nature, 461, 802-808.
20. Anney, R., Klei, L., Pinto, D., Regan, R., Conroy, J., Magalhaes, T.R., Correia, C., Abrahams, B.S., Sykes, N., Pagnamenta, A.T. et al. (2010) A genome-wide scan for common alleles affecting risk for autism. Hum. Mol. Genet., 19, 4072-4082.
21. 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) Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature, 485, 242-245.
22. Iossifov, I., O'Roak, B.J., Sanders, S.J., Ronemus, M., Krumm, N., Levy, D., Stessman, H.A., Witherspoon, K.T., Vives, L., Patterson, K.E. et al. (2014) The contribution of de novo coding mutations to autism spectrum disorder. Nature, 515, 216-221.
23. Iossifov, I., Ronemus, M., Levy, D., Wang, Z., Hakker, I., Rosenbaum, J., Yamrom, B., Lee, Y.H., Narzisi, G., Leotta, A. et al. (2012) De novo gene disruptions in children on the autistic spectrum. Neuron, 74, 285-299.
24. 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) De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature, 485, 237-241.
25. 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) Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature, 485, 246-250.
26. De Rubeis, S., He, X., Goldberg, A.P., Poultney, C.S., Samocha, K., Cicek, A.E., Kou, Y., Liu, L., Fromer, M., Walker, S. et al. (2014) Synaptic, transcriptional and chromatin genes disrupted in autism. Nature, 515, 209-215.
27. Krumm, N., O'Roak, B.J., Karakoc, E., Mohajeri, K., Nelson, B., Vives, L., Jacquemont, S., Munson, J., Bernier, R. and Eichler, E.E. (2013) Transmission disequilibrium of small CNVs in simplex autism. Am. J. Hum. Genet., 93, 595-606.
28. Krumm, N., Turner, T.N., Baker, C., Vives, L., Mohajeri, K., Witherspoon, K., Raja, A., Coe, B.P., Stessman, H.A., He, Z. X. et al. (2015) Excess of rare, inherited truncating mutations in autism. Nat. Genet., 47, 582-588.
29. Poultney, C.S., Goldberg, A.P., Drapeau, E., Kou, Y., Harony-Nicolas, H., Kajiwara, Y., De Rubeis, S., Durand, S., Stevens, C., Rehnstrom, K. et al. (2013) Identification of small exonic CNV from whole-exome sequence data and application to autism spectrum disorder. Am. J. Hum. Genet., 93, 607-619.
30. Pinto, D., Delaby, E., Merico, D., Barbosa, M., Merikangas, A., Klei, L., Thiruvahindrapuram, B., Xu, X., Ziman, R., Wang, Z. et al. (2014) Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am. J. Hum. Genet., 94, 677-694.
31. Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J. et al. (2007) Strong association of de novo copy number mutations with autism. Science, 316, 445-449.
32. Sanders, S.J., Ercan-Sencicek, A.G., Hus, V., Luo, R., Murtha, M.T., Moreno-De-Luca, D., Chu, S.H., Moreau, M.P., Gupta, A.R., Thomson, S.A. et al. (2011) Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron, 70, 863-885.
33. Dong, S., Walker, M.F., Carriero, N.J., DiCola, M., Willsey, A.J., Ye, A.Y., Waqar, Z., Gonzalez, L.E., Overton, J.D., Frahm, S. et al. (2014) De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder. Cell Reports, 9, 16-23.
34. Lim, E.T., Raychaudhuri, S., Sanders, S.J., Stevens, C., Sabo, A., MacArthur, D.G., Neale, B.M., Kirby, A., Ruderfer, D.M., Fromer, M. et al. (2013) Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders. Neuron, 77, 235-242.
35. 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) Using whole-exome sequencing to identify inherited causes of autism. Neuron, 77, 259-273.
36. Marshall, C.R., Noor, A., Vincent, J.B., Lionel, A.C., Feuk, L., Skaug, J., Shago, M., Moessner, R., Pinto, D., Ren, Y. et al. (2008) Structural variation of chromosomes in autism spectrum disorder. Am. J. Hum. Genet., 82, 477-488.
37. Levy, D., Ronemus, M., Yamrom, B., Lee, Y.H., Leotta, A., Kendall, J., Marks, S., Lakshmi, B., Pai, D., Ye, K. et al. (2011) Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron, 70, 886-897.
38. Hultman, C.M., Sandin, S., Levine, S.Z., Lichtenstein, P. and Reichenberg, A. (2011) Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies. Mol. Psychiatry, 16, 1203-1212.
39. McGrath, J.J., Petersen, L., Agerbo, E., Mors, O., Mortensen, P.B. and Pedersen, C.B. (2014) A comprehensive assessment of parental age and psychiatric disorders. JAMA Psychiatry, 71, 301-309.
40. D'Onofrio, B.M., Rickert, M.E., Frans, E., Kuja-Halkola, R., Almqvist, C., Sjolander, A., Larsson, H. and Lichtenstein, P. (2014) Paternal age at childbearing and offspring psychiatric and academic morbidity. JAMA Psychiatry, 71, 432-438.
41. Sandin, S., Schendel, D., Magnusson, P., Hultman, C., Suren, P., Susser, E., Gronborg, T., Gissler, M., Gunnes, N., Gross, R. et al. (2015) Autism risk associated with parental age and with increasing difference in age between the parents. Mol. Psychiatry, doi: 10.1038/mp.2015.70.
42. Sandin, S., Hultman, C.M., Kolevzon, A., Gross, R., MacCabe, J.H. and Reichenberg, A. (2012) Advancing maternal age is associated with increasing risk for autism: a review and meta-analysis. J. Am. Acad. Child Adolesc. Psychiatry, 51, 477-486.e471.
43. Kong, A., Frigge, M.L., Masson, G., Besenbacher, S., Sulem, P., Magnusson, G., Gudjonsson, S.A., Sigurdsson, A., Jonasdottir, A., Jonasdottir, A. et al. (2012) Rate of de novo mutations and the importance of father's age to disease risk. Nature, 488, 471-475.
44. Hehir-Kwa, J.Y., Rodriguez-Santiago, B., Vissers, L.E., de Leeuw, N., Pfundt, R., Buitelaar, J.K., Perez-Jurado, L.A. and Veltman, J.A. (2011) De novo copy number variants associated with intellectual disability have a paternal origin and age bias. J. Med. Genet., 48, 776-778.
45. Jones, K.T. (2008) Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age. Hum. Reprod. Update, 14, 143-158.
46. Gronborg, T.K., Schendel, D.E. and Parner, E.T. (2013) Recurrence of autism spectrum disorders in full-and half-siblings and trends over time: a population-based cohort study. JAMA Pediatrics, 167, 947-953.
47. Yuen, R.K., Thiruvahindrapuram, B., Merico, D., Walker, S., Tammimies, K., Hoang, N., Chrysler, C., Nalpathamkalam, T., Pellecchia, G., Liu, Y. et al. (2015) Whole-genome sequencing of quartet families with autism spectrumdisorder. Nat. Med., 21, 185-191.
48. Autism Genome Project, C. Szatmari, P., Paterson, A.D., Zwaigenbaum, L., Roberts, W., Brian, J., Liu, X.Q., Vincent, J.B., Skaug, J.L., Thompson, A.P. et al. (2007) Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat. Genet., 39, 319-328.
49. Mlynarski, E.E., Sheridan, M.B., Xie, M., Guo, T., Racedo, S.E., McDonald-McGinn, D.M., Gai, X., Chow, E.W., Vorstman, J., Swillen, A. et al. (2015) Copy-number variation of the glucose transporter gene SLC2A3 and congenital heart defects in the 22q11.2 deletion syndrome. Am. J. Hum. Genet., 96, 753-764.
50. Moreno-De-Luca, A., Evans, D.W., Boomer, K.B., Hanson, E., Bernier, R., Goin-Kochel, R.P., Myers, S.M., Challman, T.D., Moreno-De-Luca, D., Slane, M.M. et al. (2015) The role of parental cognitive, behavioral, and motor profiles in clinical variability in individuals with chromosome 16p11.2 deletions. JAMA Psychiatry, 72, 119-126.
51. He, X., Sanders, S.J., Liu, L., De Rubeis, S., Lim, E.T., Sutcliffe, J.S., Schellenberg, G.D., Gibbs, R.A., Daly, M.J., Buxbaum, J.D. et al. (2013) Integrated model of de novo and inherited genetic variants yields greater power to identify risk genes. PLoS Genet., 9, e1003671.
52. Sugathan, A., Biagioli, M., Golzio, C., Erdin, S., Blumenthal, I., Manavalan, P., Ragavendran, A., Brand, H., Lucente, D., Miles, J. et al. (2014) CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors. Proc. Natl Acad. Sci. USA, 111, E4468-E4477.
53. Cotney, 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) The autismassociated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment. Nat. Commun., 6, 6404.
54. Wilkinson, B., Grepo, N., Thompson, B.L., Kim, J., Wang, K., Evgrafov, O.V., Lu, W., Knowles, J.A. and Campbell, D.B. (2015) The autism-associated gene chromodomain helicase DNA-binding protein 8 (CHD8) regulates noncoding RNAs and autism-related genes. Transl. Psychiatry, 5, e568.
55. Nishiyama, M., Oshikawa, K., Tsukada, Y., Nakagawa, T., Iemura, S., Natsume, T., Fan, Y., Kikuchi, A., Skoultchi, A.I. and Nakayama, K.I. (2009) CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis. Nat. Cell Biol., 11, 172-182.
56. Bernier, R., Golzio, C., Xiong, B., Stessman, H.A., Coe, B.P., Penn, O., Witherspoon, K., Gerdts, J., Baker, C., Vulto-van Silfhout, A.T. et al. (2014) Disruptive CHD8 mutations define a subtype of autism early in development. Cell, 158, 263-276.
57. Nishiyama, M., Nakayama, K., Tsunematsu, R., Tsukiyama, T., Kikuchi, A. and Nakayama, K.I. (2004) Early embryonic death in mice lacking the beta-catenin-binding protein Duplin. Mol. Cell. Biol., 24, 8386-8394.
58. Mandel, S. and Gozes, I. (2007) Activity-dependent neuroprotective protein constitutes a novel element in the SWI/SNF chromatin remodeling complex. J. Biol. Chem., 282, 34448-34456.
59. Mandel, S., Rechavi, G. and Gozes, I. (2007) Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate genes essential for embryogenesis. Dev. Biol., 303, 814-824.
60. Merenlender-Wagner, A., Malishkevich, A., Shemer, Z., Udawela, M., Gibbons, A., Scarr, E., Dean, B., Levine, J., Agam, G. and Gozes, I. (2015) Autophagy has a key role in the pathophysiology of schizophrenia. Mol. Psychiatry, 20, 126-132.
61. Oz, S., Kapitansky, O., Ivashco-Pachima, Y., Malishkevich, A., Giladi, E., Skalka, N., Rosin-Arbesfeld, R., Mittelman, L., Segev, O., Hirsch, J.A. et al. (2014) The NAP motif of activitydependent neuroprotective protein (ADNP) regulates dendritic spines through microtubule end binding proteins. Mol. Psychiatry, 19, 1115-1124.
62. Furman, S., Steingart, R.A., Mandel, S., Hauser, J.M., Brenneman, D.E. and Gozes, I. (2004) Subcellular localization and secretion of activity-dependent neuroprotective protein in astrocytes. Neuron. Glia Biol., 1, 193-199.
63. Dresner, E., Malishkevich, A., Arviv, C., Leibman Barak, S., Alon, S., Ofir, R., Gothilf, Y. and Gozes, I. (2012) Novel evolutionary-conserved role for the activity-dependent neuroprotective protein (ADNP) family that is important for erythropoiesis. J. Biol. Chem., 287, 40173-40185.
64. Pinhasov, A., Mandel, S., Torchinsky, A., Giladi, E., Pittel, Z., Goldsweig, A.M., Servoss, S.J., Brenneman, D.E. and Gozes, I. (2003) Activity-dependent neuroprotective protein: a novel gene essential for brain formation. Brain Res. Dev. Brain Res., 144, 83-90.
65. Vulih-Shultzman, I., Pinhasov, A., Mandel, S., Grigoriadis, N., Touloumi, O., Pittel, Z. and Gozes, I. (2007) Activity-dependent neuroprotective protein snippet NAP reduces tau hyperphosphorylation and enhances learning in a novel transgenic mouse model. J. Pharmacol. Exp. Ther., 323, 438-449.
66. Malishkevich, A., Amram, N., Hacohen-Kleiman, G., Magen, I., Giladi, E. and Gozes, I. (2015) Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer's pathologies. Transl. Psychiatry, 5, e501.
67. Helsmoortel, C., Vulto-van Silfhout, A.T., Coe, B.P., Vandeweyer, G., Rooms, L., van den Ende, J., Schuurs-Hoeijmakers, J.H., Marcelis, C.L., Willemsen, M.H., Vissers, L.E. et al. (2014) A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP. Nat. Genet., 46, 380-384.
68. Hevner, R.F., Shi, L., Justice, N., Hsueh, Y., Sheng, M., Smiga, S., Bulfone, A., Goffinet, A.M., Campagnoni, A.T. and Rubenstein, J.L. (2001) Tbr1 regulates differentiation of the preplate and layer 6. Neuron, 29, 353-366.
69. Bedogni, F., Hodge, R.D., Elsen, G.E., Nelson, B.R., Daza, R.A., Beyer, R.P., Bammler, T.K., Rubenstein, J.L. and Hevner, R.F. (2010) Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex. Proc. Natl Acad. Sci. USA, 107, 13129-13134.
70. Englund, C., Fink, A., Lau, C., Pham, D., Daza, R.A., Bulfone, A., Kowalczyk, T. and Hevner, R.F. (2005) Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J. Neurosci., 25, 247-251.
71. Bulfone, A., Wang, F., Hevner, R., Anderson, S., Cutforth, T., Chen, S., Meneses, J., Pedersen, R., Axel, R. and Rubenstein, J.L. (1998) An olfactory sensory map develops in the absence of normal projection neurons or GABAergic interneurons. Neuron, 21, 1273-1282.
72. Huang, T.N., Chuang, H.C., Chou, W.H., Chen, C.Y., Wang, H.F., Chou, S.J. and Hsueh, Y.P. (2014) Tbr1 haploinsufficiency impairs amygdalar axonal projections and results in cognitive abnormality. Nat. Neurosci., 17, 240-247.
73. Hamdan, F.F., Srour, M., Capo-Chichi, J.M., Daoud, H., Nassif, C., Patry, L., Massicotte, C., Ambalavanan, A., Spiegelman, D., Diallo, O. et al. (2014) De novo mutations in moderate or severe intellectual disability. PLoS Genet., 10, e1004772.
74. Galiano, M.R., Jha, S., Ho, T.S., Zhang, C., Ogawa, Y., Chang, K.J., Stankewich, M.C., Mohler, P.J. and Rasband, M.N. (2012) A distal axonal cytoskeleton forms an intra-axonal boundary that controls axon initial segment assembly. Cell, 149, 1125-1139.
75. Chang, K.J., Zollinger, D.R., Susuki, K., Sherman, D.L., Makara, M.A., Brophy, P.J., Cooper, E.C., Bennett, V., Mohler, P.J. and Rasband, M.N. (2014) Glial ankyrins facilitate paranodal axoglial junction assembly. Nat. Neurosci., 17, 1673-1681.
76. Scotland, P., Zhou, D., Benveniste, H. and Bennett, V. (1998) Nervous system defects of AnkyrinB (-/-) mice suggest functional overlap between the cell adhesion molecule L1 and 440-kD AnkyrinB in premyelinated axons. J. Cell Biol., 143, 1305-1315.
77. Tuvia, S., Buhusi, M., Davis, L., Reedy, M. and Bennett, V. (1999) Ankyrin-B is required for intracellular sorting of structurally diverse Ca2+ homeostasis proteins. J. Cell Biol., 147, 995-1008.
78. Mohler, P.J., Schott, J.J., Gramolini, A.O., Dilly, K.W., Guatimosim, S., duBell, W.H., Song, L.S., Haurogne, K., Kyndt, F., Ali, M.E. et al. (2003) Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. Nature, 421, 634-639.
79. Smith, S.A., Sturm, A.C., Curran, J., Kline, C.F., Little, S.C., Bonilla, I.M., Long, V.P., Makara, M., Polina, I., Hughes, L.D. et al. (2015) Dysfunction in the betaII spectrin-dependent cytoskeleton underlies human arrhythmia. Circulation, 131, 695-708.
80. Willsey, A.J., Sanders, S.J., Li, M., Dong, S., Tebbenkamp, A.T., Muhle, R.A., Reilly, S.K., Lin, L., Fertuzinhos, S., Miller, J.A. et al. (2013) Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell, 155, 997-1007.
81. Shen, T., Ji, F., Yuan, Z. and Jiao, J. (2015) CHD2 is required for embryonic neurogenesis in the developing cerebral cortex. Stem Cells, 33, 1794-1806.
82. Suls, A., Jaehn, J.A., Kecskes, A., Weber, Y., Weckhuysen, S., Craiu, D.C., Siekierska, A., Djemie, T., Afrikanova, T., Gormley, P. et al. (2013) De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome. Am. J. Hum. Genet., 93, 967-975.
83. Galizia, E.C., Myers, C.T., Leu, C., de Kovel, C.G., Afrikanova, T., Cordero-Maldonado, M.L., Martins, T.G., Jacmin, M., Drury, S., Krishna Chinthapalli, V. et al. (2015) CHD2 variants are a risk factor for photosensitivity in epilepsy. Brain, 138, 1198-1207.
84. Marfella, C.G., Ohkawa, Y., Coles, A.H., Garlick, D.S., Jones, S.N. and Imbalzano, A.N. (2006) Mutation of the SNF2 family member Chd2 affects mouse development and survival. J. Cell. Physiol., 209, 162-171.
85. Kulkarni, S., Nagarajan, P., Wall, J., Donovan, D.J., Donell, R.L., Ligon, A.H., Venkatachalam, S. and Quade, B.J. (2008) Disruption of chromodomain helicase DNA binding protein 2 (CHD2) causes scoliosis. Am. J. Med. Genet. A, 146A, 1117-1127.
86. Marfella, C.G., Henninger, N., LeBlanc, S.E., Krishnan, N., Garlick, D.S., Holzman, L.B. and Imbalzano, A.N. (2008) A mutation in the mouse Chd2 chromatin remodeling enzyme results in a complex renal phenotype. Kidney Blood Press. Res., 31, 421-432.
87. Epi4K Consortium; Epilepsy Phenome/Genome Project, Allen, A.S., Berkovic, S.F., Cossette, P., Delanty, N., Dlugos, D., Eichler, E.E., Epstein, M.P., Glauser, T. et al. (2013) De novo mutations in epileptic encephalopathies. Nature, 501, 217-221.
88. Cunha, S.R. and Mohler, P.J. (2006) Cardiac ankyrins: essential components for development and maintenance of excitable membrane domains in heart. Cardiovasc. Res., 71, 22-29.
89. Carvill, G.L., Heavin, S.B., Yendle, S.C., McMahon, J.M., O'Roak, B.J., Cook, J., Khan, A., Dorschner, M.O., Weaver, M., Calvert, S. et al. (2013) Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nat. Genet., 45, 825-830.
90. Chenier, S., Yoon, G., Argiropoulos, B., Lauzon, J., Laframboise, R., Ahn, J.W., Ogilvie, C.M., Lionel, A.C., Marshall, C. R., Vaags, A.K. et al. (2014) CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems. J. Neurodev. Disord., 6, 9.
91. Buxbaum, J.D., Betancur, C., Bozdagi, O., Dorr, N.P., Elder, G. A. and Hof, P.R. (2012) Optimizing the phenotyping of rodent ASD models: enrichment analysis of mouse and human neurobiological phenotypes associated with high-risk autism genes identifies morphological, electrophysiological, neurological, and behavioral features. Mol. Autism, 3, 1.
92. Li, J., Cai, T., Jiang, Y., Chen, H., He, X., Chen, C., Li, X., Shao, Q., Ran, X., Li, Z. et al. (2015) Genes with de novo mutations are shared by four neuropsychiatric disorders discovered from NPdenovo database. Mol. Psychiatry, doi: 10.1038/mp.2015.58.
93. Buxbaum, J.D. (2015) DSM-5 and psychiatric genetics-round hole, meet square peg. Biol. Psychiatry, 77, 766-768.
94. Zaidi, S., Choi, M., Wakimoto, H., Ma, L., Jiang, J., Overton, J. D., Romano-Adesman, A., Bjornson, R.D., Breitbart, R.E., Brown, K.K. et al. (2013) De novo mutations in histone-modifying genes in congenital heart disease. Nature, 498, 220-223.
95. Moreno-De-Luca, A., Myers, S.M., Challman, T.D., Moreno-De-Luca, D., Evans, D.W. and Ledbetter, D.H. (2013) Developmental brain dysfunction: revival and expansion of old concepts based on new genetic evidence. Lancet Neurol., 12, 406-414.
96. Bassett, A.S., McDonald-McGinn, D.M., Devriendt, K., Digilio, M.C., Goldenberg, P., Habel, A., Marino, B., Oskarsdottir, S., Philip, N., Sullivan, K. et al. (2011) Practical guidelines for managing patients with 22q11.2 deletion syndrome. J. Pediatr., 159, 332-339 e331.
97. Samocha, K.E., Robinson, E.B., Sanders, S.J., Stevens, C., Sabo, A., McGrath, L.M., Kosmicki, J.A., Rehnström, K., Mallick, S., Kirby, A. et al. (2014) A framework for the interpretation of de novo mutation in human disease. Nat. Genet., 46, 944-950.
98. Robinson, E.B., Samocha, K.E., Kosmicki, J.A., McGrath, L., Neale, B.M., Perlis, R.H. and Daly, M.J. (2014) Autism spectrum disorder severity reflects the average contribution of de novo and familial influences. Proc. Natl Acad. Sci. USA, 111, 15161-15165.
99. Veatch, O.J., Veenstra-Vanderweele, J., Potter, M., Pericak-Vance, M.A. and Haines, J.L. (2014) Genetically meaningful phenotypic subgroups in autism spectrum disorders. Genes Brain Behav., 13, 276-285.
100. Hus, V., Pickles, A., Cook, E.H. Jr, Risi, S. and Lord, C. (2007) Using the autism diagnostic interview-revised to increase phenotypic homogeneity in genetic studies of autism. Biol. Psychiatry, 61, 438-448.
101. Bishop, S.L., Hus, V., Duncan, A., Huerta, M., Gotham, K., Pickles, A., Kreiger, A., Buja, A., Lund, S. and Lord, C. (2013) Subcategories of restricted and repetitive behaviors in children with autism spectrum disorders. J. Autism Dev. Disord., 43, 1287-1297.
102. Liu, X.Q., Paterson, A.D. and Szatmari, P; Autism Genome Project Consortium. (2008) Genome-wide linkage analyses of quantitative and categorical autism subphenotypes. Biol. Psychiatry, 64, 561-570.
103. Vieland, V.J., Hallmayer, J., Huang, Y., Pagnamenta, A.T., Pinto, D., Khan, H., Monaco, A.P., Paterson, A.D., Scherer, S. W., Sutcliffe, J.S. et al. (2011) Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism. J. Neurodev. Disord., 3, 113-123.
104. Chaste, P., Klei, L., Sanders, S.J., Hus, V., Murtha, M.T., Lowe, J.K., Willsey, A.J., Moreno-De-Luca, D., Yu, T.W., Fombonne, E. et al. (2015) A genome-wide association study of autism using the Simons Simplex Collection: does reducing phenotypic heterogeneity in autism increase genetic homogeneity? Biol. Psychiatry, 77, 775-784.
105. Buxbaum, J.D. (2015) DSM-5 and psychiatric genetics-round hole, meet square peg. Biol. Psychiatry, 77, 766-768.
106. Gillberg, C. (2010) The ESSENCE in child psychiatry: early symptomatic syndromes eliciting neurodevelopmental clinical examinations. Res. Dev. Disabil., 31, 1543-1551.