孤独症谱系障碍基因组学生物学标记物的研究进展

doi:10.11852/zgetbjzz2019-0762

摘要/Abstract

摘要： 孤独症谱系障碍(ASD)是一种以社会交往障碍、狭隘兴趣和刻板重复行为模式为特征的神经发育障碍性疾病,近年来发病率明显上升,达到1∶59,至今病因及发病机制未明。早期诊断及早期干预对ASD儿童的康复至关重要。近年ASD的生物学标记物研究取得很大进展,尤其是基因组学方面,包括基因突变、拷贝数变异、单核苷酸多态性和表观遗传。本文将对ASD基因组学生物学标记物的研究进展进行综述。

关键词: 孤独症谱系障碍, 生物学标记物, 拷贝数变异, 表观遗传

Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by impairment social interaction,repetitive behaviors and restricted interest. Recent studies have demonstrated dramatically increasing prevalence of ASD,reaching to 1∶59. However,the etiology and pathogenesis of ASD remain unknown. Early diagnosis and early intervention are crucial to the rehabilitation of ASD. In recent years,researches on biological markers of ASD has made great progress,especially in genomics,including gene mutation,copy number variation,single nucleotide polymorphism and epigenetic. This review will summarize the research progress on genomic biomarkers of ASD.

Key words: autism spectrum disorders, biomarker, copy number variant, epigenetic

中图分类号:

R749.94

韦念堇, 王瑜. 孤独症谱系障碍基因组学生物学标记物的研究进展[J]. 中国儿童保健杂志, 2020, 28(5): 551-554.

WEI Nian-jin, WANG Yu. Research advances on the genomic biomarkers of autism spectrum disorder[J]. journal1, 2020, 28(5): 551-554.

参考文献

[1] Loomes R,Hull L,Mandy WPL.What is the male-to-female ratio in autism spectrum disorder? A systematic review and meta-analysis[J].J Am Acad Child Adolesc Psychiatry,2017,56(6):466-474.
[2] Baio J,Wiggins L,Christensen DL,et al.Prevalence of autism spectrum disorder among children aged 8 years-autism and developmental disabilities monitoring network,11 sites,United States,2014[J].MMWR Surveill Summ,2018,67(6):1-23.
[3] Bourgeron T.Current knowledge on the genetics of autism a nd propositions for future research[J].Comptes Rendus Biologies,2016,339:300-307.
[4] Buescher AVS,Cidav Z,Knapp M,et al.Costs of autism sp ectrum disorders in the United Kingdom and the United States[J].JAMA Pediatrics,2014,168(8):721-728.
[5] Landa RJ.Efficacy of early interventions for infants and yo-ung children with,and at risk for,autism spectrum disorders[J].Int Rev Psychiatry,2018,30(1):25-39.
[6] Yu L,Wu Y,Wu BL.Genetic architecture,epigenetic influence and environment exposure in the pathogenesis of Autism[J].Sci China Life Sci,2015,58(10):958-967.
[7] Chen JA,Penagarikano O,Belgard TG,et al.The emerging picture of autism spectrum disorder:genetics and pathology[J].Annu Rev Pathol,2015,10:111-144.
[8] Rk CY,Merico D,Bookman M,et al.Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder[J].Nat Neurosci,2017,20(4):602-611.
[9] Liska A,Bertero A,Gomolka R,et al.Homozygous loss of autism-risk gene CNTNAP2 results in reduced local and long-range prefrontal functional connectivity[J].Cereb Cortex,2018,28(4):1141-1153.
[10] Van Dijck A,Vulto-van Silfhout AT,Cappuyns E,et al.Clinical presentation of a complex neurodevelopmental disorder caused by mutations in ADNP[J].Biol Psychiatry,2019,85(4):287-297.
[11] Jang W,Kim Y,Han E,et al.Chromosomal microarray analysis as a first-tier clinical diagnostic test in patients with developmental delay/Intellectual disability,autism spectrum disorders,and multiple congenital anomalies:a prospective multicenter study in korea[J].Annals of Laboratory Medicine,2019,39(3):299.
[12] Carter MT,Scherer Sw.Autism spectrum disorder in the genetics clinic:a review[J].Clin Genet,2013,83(5):399-407.
[13] Vatsa N,Jana NR.UBE3A and its link with autism[J].Front Mol Neurosci,2018,11:448.
[14] Bertero A,Liska A,Pagani M,et al.Autism-associated 16p11.2 microdeletion impairs prefrontal functional connectivity in mouse and human[J].Brain,2018,141(7):2055-2065.
[15] 何学莲,赵培伟,黄玉凤,等.一例孤独症患儿的全基因组拷贝数变异分析 [J].中华医学遗传学杂志,2019,36(2):157-160.
[16] Gorker I,Gurkan H,Ulusal S,et al.Investigation of copy number variation by arrayCGH in Turkish children and adolescents diagnosed with autism spectrum disorders[J].Noropsikiyatri Arsi,2018,55(3):215-219.
[17] Zou M,Sun C,Liang S,et al.Fisher discriminant analysis for classification of autism spectrum disorders based on folate-related metabolism markers[J].J Nutr Biochem,2019,64:25-31.
[18] Rai V.Association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with autism:evidence of genetic susceptibility[J].Metab Brain Dis,2016,31(4):727-735.
[19] Aoki Y,Cortese S.Mitochondrial Aspartate/Glutamate Ca-rrier SLC25A12 and Autism Spectrum Disorder:a Meta-Analysis[J].Mol Neurobiol,2016,53(3):1579-1588.
[20] Mashayekhi F,Mizban N,Bidabadi E,et al.The association of SHANK3 gene polymorphism and autism[J].Minerva Pediatr,2016.PMID:27271042.
[21] Mahdavi M,Kheirollahi M,Riahi R,et al.Meta-analysis of the association between GABA receptor polymorphisms and autism spectrum disorder (ASD)[J].J Mol Neurosci,2018,65(1):1-9.
[22] Siu MT,Weksberg R.Epigenetics of autism spectrum disorder[J].Adv Exp Med Biol,2017,978:63-90.
[23] Vicari S,Napoli E,Cordeddu V,et al.Copy number variants in autism spectrum disorders[J].Prog in neuro-psychoph,2019,92:421-427.
[24] Lyko F.The DNA methyltransferase family:a versatile to-olkit for epigenetic regulation[J].Nat Rev Genet,2018,19(2):81-92.
[25] Wu XJ,Zhang Y.TET-mediated active DNA demethylation:mechanism,function and beyond[J].Nat Rev Genet,2017,18(9):517-534.
[26] Tremblay MW,Jiang Y-h.DNA methylation and susceptibility to autism spectrum disorder[J].Annu Rev of Med,2019,70:151-166.
[27] Fasolino M,Zhou Z.The crucial role of DNA methylation and MeCP2 in neuronal function[J].Genes (Basel),2017,8(5).DOI:10.3390/genes8050141.
[28] 徐萍,张静洁,季卫东,等.血清脑源性神经营养因子及其基因启动子甲基化水平与儿童孤独症谱系障碍的关联性分析[J].中国临床药理学杂志,2018,34(21):2510-2512.
[29] Zhubi A,Chen Y,Guidotti A,et al.Epigenetic regulation of RELN and GAD1 in the frontal cortex (FC) of autism spectrum disorder (ASD) subjects[J].Int J Dev Neurosci,2017,62:63-72.
[30] Wapinski O,Chang HY.Long noncoding RNAs and human disease[J].Trends Cell Biol,2011,21(6):354-361.
[31] Parikshak NN,Swarup V,Belgard TG,et al.Genome-wide changes in lncRNA,splicing,and regional gene expression patterns in autism[J].Nature,2016,540(7633):423-427.
[32] Wang Y,Zhao X,Ju W,et al.Genome-wide differential expression of synaptic long noncoding RNAs in autism spectrum disorder[J].Transl Psychiatry,2015,5:e660.
[33] Ang CE,Ma Q,Wapinski OL,et al.The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders[J].Elife,2019.DOI:10.7554/eLife.41770.
[34] Monteiro P,Feng G.SHANK proteins:roles at the synapse and in autism spectrum disorder[J].Nat Rev Neurosci,2017,18(3):147-157.
[35] Cao X,Tabuchi K.Functions of synapse adhesion molecules neurexin/neuroligins and neurodevelopmental disorders[J].Neurosci Res,2017,116:3-9.
[36] Bernier R,Golzio C,Xiong B,et al.Disruptive CHD8 mutations define a subtype of autism early in development[J].Cell,2014,158(2):263-276.
[37] Kwan V,Unda BK,Singh KK.Wnt signaling networks in autism spectrum disorder and intellectual disability[J].J Neurodev Disord,2016,8:45.
[38] Borrie SC,Brems H,Legius E,et al.Cognitive dysfunctions in intellectual disabilities:the contributions of the ras-MAPK and PI3K-AKT-mTOR Pathways[J].Annu Rev Genomics Hum Genet,2017,18:115-142.
[39] Yeung KS,Tso WWY,Ip JJK,et al.Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism[J].Mol Autism,2017,8:66.
[40] Woodbury-Smith M,Scherer SW.Progress in the genetics of autism spectrum disorder[J].Dew Med Child Neurol,2018,60(5):445-451.