Abstract：Autism spectrum disorder (ASD) is a kind of neurodevelopmental multigenic disorder. More than one hundred of candidate genes for ASD have been reported. The candidate gene research for ASD involves in chromosome loci and screening of candidate genes and epigenetic abnormalities for candidate genes. The reported genes encode neural adhesion molecules, ion channels, scaffold proteins, protein kinases, receptor protein and carrier protein, signaling modulate molecules and circadian relevant proteins. The research of mutation screening and expression regulation of candidate genes can help to elucidate genetic mechanisms for ASD, and may provide new approaches for the diagnosis and treatment of this disorder. This article reviews the research advance in candidate genes for ASD.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders[M]. 5th ed. Arlington, VA: American Psychiatric Publishing, 2013: 50-59.
[2]
Çöp E, Yurtbaşi P, Öner Ö, et al. Genetic testing in children with autism spectrum disorders[J]. Anadolu Psikiyatri Derg, 2015, 16(6): 426-432.
[3]
Luo R, Sanders SJ, Tian Y, et al. Genome-wide transcriptome profiling reveals the functional impact of rare de novo and recurrent CNVs in autism spectrum disorders[J]. Am J Hum Genet, 2012, 91(1): 38-55.
[4]
Abu-Amero KK, Hellani AM, Salih MA, et al. A de novo marker chromosome derived from 9p in a patient with 9p partial duplication syndrome and autism features: genotype-phenotype correlation[J]. BMC Med Genet, 2010, 11(9): 135-142.
[5]
Sanders SJ, Ercan-Sencicek AG, Hus V, et al. Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism[J]. Neuron, 2011, 70(5): 863-885.
[6]
Betancur C. Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting[J]. Brain Res, 2011, 1380(3): 42-77.
[7]
Morrow EM, Yoo SY, Flavell SW, et al. Identifying autism loci and genes by tracing recent shared ancestry[J]. Science, 2008, 321(5886): 218-223.
[8]
Jamain S, Quach H, Betancur C, et al. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism[J]. Nat Genet, 2003, 34(1): 27-29.
[9]
Glessner JT, Wang K, Cai G, et al. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes[J]. Nature, 2009, 459(7246): 569-573.
[10]
Zhiling Y, Fujita E, Tanabe Y, et al. Mutations in the gene encoding CADM1 are associated with autism spectrum disorder[J]. Biochem Biophys Res Commun, 2008, 377(3): 926-929.
[11]
Roohi J, Montagna C, Tegay DH, et al. Disruption of contactin 4 in three subjects with autism spectrum disorder[J]. J Med Genet, 2009, 46(3): 176-182.
[12]
Alarcón M, Abrahams BS, Stone JL, et al. Linkage, association, and gene-expression analyses identify CNTNAP2 as an autismsusceptibility gene[J]. Am J Hum Genet, 2008, 82(1): 150-159.
[13]
Babatz TD, Kumar RA, Sudi J, et al. Copy number and sequence variants implicate APBA2 as an autism candidate gene[J]. Autism Res, 2009, 2(6): 359-364.
[14]
Redies C, Hertel N, Hübner CA. Cadherins and neuropsychiatric disorders[J]. Brain Res, 2012, 1470(8): 130-144.
[15]
De Wolf V, Crepel A, Schuit F, et al. A complex Xp11.22 deletion in a patient with syndromic autism: exploration of FAM120C as a positional candidate gene for autism[J]. Am J Med Genet A, 2014, 164A(12): 3035-3041.
[16]
Fujita E, Tanabe Y, Imhof BA, et al. Cadm1-expressing synapses on Purkinje cell dendrites are involved in mouse ultrasonic vocalization activity[J]. PLoS One, 2012, 7(1): 1-7.
[17]
Li BM, Liu XR, Yi YH, et al. Autism in Dravet syndrome: prevalence, features, and relationship to the clinical characteristics of epilepsy and mental retardation[J]. Epilepsy Behav, 2011, 21(3): 291-295.
[18]
Han S, Tai C, Westenbroek RE, et al. Autistic-like behaviour in Scn1a+/- mice and rescue by enhanced GABA-mediated neurotransmission[J]. Nature, 2012, 489(7416): 385-390.
[19]
Tavassoli T, Kolevzon A, Wang AT, et al. De novo SCN2A splice site mutation in a boy with autism spectrum disorder[J]. BMC Med Genet, 2014, 15(3): 35-45.
[20]
Liao P, Soong TW. CaV1.2 channelopathies: from arrhythmias to autism, bipolar disorder, and immunodeficiency[J]. Pflugers Arch, 2010, 460(2): 353-359.
[21]
Laumonnier F, Roger S, Guérin P, et al. Association of a functional deficit of the BKCa channel,a synaptic regulator of neuronal excitability, with autism and mental retardation[J]. Am J Psychiatry, 2006, 163(9): 1622-1629.
[22]
Sato D, Lionel AC, Leblond CS, et al. SHANK1 deletions in males with autism spectrum disorder[J]. Am J Hum Genet, 2012, 90(5): 879-887.
[23]
Sicca F, Imbrici P, D'Adamo MC, et al. Autism with seizures and intellectual disability: possible causative role of gain-of-function of the inwardly-rectifying K+ channel Kir4.1[J]. Neurobiol Dis, 2011, 43(1): 239-247.
[24]
Neale BM, Kou Y, Liu L, et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders[J]. Nature, 2012, 485(7397): 242-245.
[25]
Kitagishi Y, Minami A, Nakanishi A, et al. Neuron membrane trafficking and protein kinases involved in autism and ADHD[J].Int J Mol Sci, 2015, 16(2): 3095-3115.
[26]
Berryer MH, Hamdan FF, Klitten LL, et al. Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency[J]. Hum Mutat, 2013, 34(2): 385-394.
[27]
Banerjee S, Riordan M, Bhat MA. Genetic aspects of autism spectrum disorders: insights from animal models[J]. Front Cell Neurosci, 2014, 8(2): 58-87.
[28]
Yoo HJ, Lee SK, Park M, et al. Family-and populationbased association studies of monoamine oxidase A and autism spectrum disorders in Korean[J]. Neurosci Res, 2009, 63(3): 172-176.
[29]
Bortolato M, Godar SC, Alzghoul L, et al. Monoamine oxidase A and A/B knockout mice display autistic-like features[J]. Int J Neuropsychopharmacol, 2013, 16(4): 869-888.
[30]
Kondapalli KC, Hack A, Schushan M, et al. Functional evaluation of autism-associated mutations in NHE9[J]. Nat Commun, 2013, 4(11): 2510-2523.
[31]
Cotney J, Muhle RA, Sanders SJ, et al. The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment[J]. Nat Commun, 2015, 10(6): 6404-6421.
[32]
Wilkinson B, Grepo N, Thompson BL, et al. The autismassociated gene chromodomain helicase DNA-binding protein 8 (CHD8) regulates noncoding RNAs and autism-related genes[J]. Transl Psychiatry, 2015, 19(5): e568-e575.
[33]
Kleijer KT, Schmeisser MJ, Krueger DD, et al. Neurobiology of autism gene products: towards pathogenesis and drug targets[J]. Psychopharmacology (Berl), 2014, 231(6): 1037-1062.
[34]
Garg S, Green J, Leadbitter K, et al. Neurofibromatosis type 1 and autism spectrum disorder[J]. Pediatrics, 2013, 132(6): e1642-e1648.
[35]
Frazier TW, Embacher R, Tilot AK, et al. Molecular and phenotypic abnormalities in individuals with germline heterozygous PTEN mutations and autism[J]. Mol Psychiatry, 2015, 20(9): 1132-1138.
[36]
Gkogkas CG, Khoutorsky A, Ran I, et al. Autism-related deficits via dysregulated eIF4E-dependent translational control[J]. Nature, 2013, 493(7432): 371-377.
[37]
Yang Z, Matsumoto A, Nakayama K, et al. Circadian-relevant genes are highly polymorphic in autism spectrum disorder patients[J]. Brain Dev, 2016, 38(1): 91-99.
[38]
Bragin E, Chatzimichali EA, Wright CF, et al. DECIPHER: database for the interpretation of phenotype-linked plausibly pathogenic sequence and copy-number variation[J]. Nucleic Acids Res, 2014, 42(Database issue): D993-D1000.
[39]
Nicholas B, Rudrasingham V, Nash S, et al. Association of Per1 and Npas2 with autistic disorder: support for the clock genes/social timing hypothesis[J]. Mol Psychiatry, 2007, 12(6): 581-592.
[40]
Jonsson L, Ljunggren E, Bremer A, et al. Mutation screening of melatonin-related genes in patients with autism spectrum disorders[J]. BMC Med Genomics, 2010, 3: 10-18.
[41]
Chaste P, Clement N, Mercati O, et al. Identification of pathwaybiased and deleterious melatonin receptor mutants in autism spectrum disorders and in the general population[J]. PLoS One, 2010, 5(7): e11495-e11504.
[42]
Siniscalco D, Cirillo A, Bradstreet JJ, et al. Epigenetic findings in autism: new perspectives for therapy[J]. Int J Environ Res Public Health, 2013, 10(9): 4261-4273.
[43]
Luedi PP, Dietrich FS, Weidman JR, et al. Computational and experimental identification of novel human imprinted genes[J]. Genome Res, 2007, 17(12): 1723-1730.
[44]
Zhu L, Wang X, Li XL, et al. Epigenetic dysregulation of SHANK3 in brain tissues from individuals with autism spectrum disorders[J]. Hum Mol Genet, 2014, 23(6): 1563-1578.
[45]
Ladd-Acosta C, Hansen KD, Briem E, et al. Common DNA methylation alterations in multiple brain regions in autism[J]. Mol Psychiatry, 2014, 19(8): 862-871.
[46]
Ha M, Kim VN. Regulation of microRNA biogenesis[J]. Nat Rev Mol Cell Biol, 2014 , 15(8): 509-524.
[47]
Mundalil Vasu M, Anitha A, Thanseem I, et al. Serum microRNA profiles in children with autism[J]. Mol Autism, 2014, 5(7): 40-49.
[48]
Shulha HP, Cheung I, Whittle C, et al. Epigenetic signatures of autism: trimethylated H3K4 landscapes in prefrontal neurons[J]. Arch Gen Psychiatry, 2012, 69(3): 314-324.
