电压门控钙通道编码基因在孤独症谱系障碍中的研究进展

焦翠, 柳涛

中国儿童保健杂志 ›› 2021, Vol. 29 ›› Issue (1) : 47-51.

PDF(465 KB)
PDF(465 KB)
中国儿童保健杂志 ›› 2021, Vol. 29 ›› Issue (1) : 47-51. DOI: 10.11852/zgetbjzz2020-0945
综述

电压门控钙通道编码基因在孤独症谱系障碍中的研究进展

  • 焦翠, 柳涛
作者信息 +

Research progresson voltage-gated calcium channel-encoding genes in autism spectrum disorders

  • JIAO Cui, LIU Tao
Author information +
文章历史 +

摘要

孤独症谱系障碍(ASD)是一类以社交障碍和兴趣狭窄为共同症状的广泛性神经发育障碍,发病机制主要与遗传因素有关,研究ASD易感基因是现今国内外医学领域的热点。电压门控钙离子通道(VGCC)对调控神经元动作电位的产生和神经递质的释放等至关重要。目前VGCC的10种亚型均被发现与ASD相关。本文主要综述了编码VGCC的10种基因与ASD研究工作的进展。

Abstract

Autism spectrum disorder (ASD) is a generalized neurodevelopmental disorder with social disorders and narrow interest as common symptoms.Genetic contributions are its main pathogenesis.Research on ASD susceptibility genes is a hot topic in the medical field at home and abroad.Voltage-gated calcium channels (VGCC) are essential for the regulation of neuronal action potential and neurotransmitter release.Currently,all 10 subtypes of the VGCC encoding genes have been found to be associated with ASD.So this review aims to summarize the research progress of the 10 genes encoding VGCC and ASD.

关键词

电压门控钙通道 / 孤独症谱系障碍 / 编码基因

Key words

voltage-gated calcium channel / autism spectrum disorders / encoding gene

引用本文

导出引用
焦翠, 柳涛. 电压门控钙通道编码基因在孤独症谱系障碍中的研究进展[J]. 中国儿童保健杂志. 2021, 29(1): 47-51 https://doi.org/10.11852/zgetbjzz2020-0945
JIAO Cui, LIU Tao. Research progresson voltage-gated calcium channel-encoding genes in autism spectrum disorders[J]. Chinese Journal of Child Health Care. 2021, 29(1): 47-51 https://doi.org/10.11852/zgetbjzz2020-0945
中图分类号: R749.94   

参考文献

[1] Hodges H,Fealko C,Soares N.Autism spectrum disorder:definition,epidemiology,causes,and clinical evaluation[J].Transl Pediatr,2020,9(Suppl 1):55-65.
[2] 刘贤,林穗方,陈文雄,等.中国儿童孤独症谱系障碍患病率Meta分析[J].中国儿童保健杂志,2018,25(4):402-406,429.
[3] Bai D,Yip BHK,Windham GC,et al.Association of genetic and environmental factors with autism in a 5-country cohort[J].JAMA Psychiatry,2019,76(10):1035-1043.
[4] Andrade A,Brennecke A,Mallat S,et al.Genetic associations between voltage-gated calcium channels and psychiatric disorders[J].Int J Mol Sci,2019,20(14):E3537.
[5] Zhou J,Park CY,Theesfeld CL,et al.Whole-genome deep-learning analysis identifies contribution of noncoding mutations to autism risk[J].Nat Genet,2019,51(6):973-980.
[6] Myers RA,Casals F,Gauthier J,et al.A population genetic approach to mapping neurological disorder genes using deep resequencing[J].PLoS Genet,2011,7(2):e1001318.
[7] Sykes L,Clifton NE,Hall J,et al.Regulation of the expression of the psychiatric risk gene cacna1c during associative learning[J].Mol Neuropsychiatry,2018,4(3):149-157.
[8] Splawski I,Timothy KW,Sharpe LM,et al.Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism[J].Cell,2004,119(1):19-31.
[9] Lu AT,Dai X,Martinez-Agosto JA,et al.Support for calcium channel gene defects in autism spectrum disorders[J].Mol Autism,2012,3(1):18.
[10] Skafidas E,Testa R,Zantomio D,et al.Predicting the diagnosis of autism spectrum disorder using gene pathway analysis[J].Mol Psychiatry,2014,19(4):504-510.
[11] Li J,Zhao L,You Y,et al.Schizophrenia related variants in CACNA1C also confer risk of autism[J].PLoS One,2015,10(7):e0133247.
[12] Sayad A,Ghafouri-Fard S,Noroozi R,et al.Association study of sequence variants in voltage-gated Ca2+ channel subunit alpha-1C and autism spectrum disorders[J].Rep Biochem Mol Biol,2019,8(1):56-62.
[13] Kisko TM,Braun MD,Michels S,et al.Cacna1c haploinsufficiency leads to pro-social 50-kHz ultrasonic communication deficits in rats[J].Dis Model Mech,2018,11(6):dmm034116.
[14] Bader PL,Faizi M,Kim LH,et al.Mouse model of Timothy syndrome recapitulates triad of autistic traits[J].Proc Natl Acad Sci USA,2011,108(37):15432-15437.
[15] Calorio C,Gavello D,Guarina L,et al.Impaired chromaffin cell excitability and exocytosis in autistic Timothy syndrome TS2-neo mouse rescued by L-type calcium channel blockers[J].J Physiol,2019,597(6):1705-1733.
[16] Boczek NJ,Miller EM,Ye D,et al.Novel Timothy syndrome mutation leading to increase in CACNA1C window current[J].Heart Rhythm,2015,12(1):211-219.
[17] O'roak BJ,Vives L,Girirajan S,et al.Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations[J].Nature,2012,485(7397):246-250.
[18] Pinggera A,Negro G,Tuluc P,et al.Gating defects of disease-causing de novo mutations in Ca(v)1.3 Ca(2+) channels[J].Channels(Austin,Tex.),2018,12(1):388-402.
[19] Wong WR,Brugman KI,Maher S,et al.Autism-associated missense genetic variants impact locomotion and neurodevelopment in Caenorhabditis elegans[J].Hum Mol Genet,2019,28(13):2271-2281.
[20] Kabir ZD,Martinez-Rivera A,Rajadhyaksha AM.From gene to behavior:L-type calcium channel mechanisms underlying neuropsychiatric symptoms[J].Neurotherapeutics,2017,14(3):588-613.
[21] Pinggera A,Lieb A,Benedetti B,et al.CACNA1D de novo mutations in autism spectrum disorders activate Cav1.3 L-type calcium channels[J].Biol Psychiatry,2015,77(9):816-822.
[22] Pinggera A,Mackenroth L,Rump A,et al.New gain-of-function mutation shows CACNA1D as recurrently mutated gene in autism spectrum disorders and epilepsy[J].Hum Mol Genet,2017,26(15):2923-2932.
[23] Iossifov I,O'roak BJ,Sanders SJ,et al.The contribution of de novo coding mutations to autism spectrum disorder[J].Nature,2014,515(7526):216-221.
[24] Epperson MV,Haws ME,Standridge SM,et al.An atypical rett syndrome phenotype due to a novel missense mutation in CACNA1A[J].J Child Neurol,2018,33(4):286-289.
[25] Li J,You Y,Yue W,et al.Genetic evidence for possible involvement of the calcium channel gene CACNA1A in autism pathogenesis in Chinese Han population[J].PLoS One,2015,10(11):e0142887.
[26] Mallmann RT,Elgueta C,Sleman F,et al.Ablation of Ca(V)2.1 voltage-gated Ca(2)(+) channels in mouse forebrain generates multiple cognitive impairments[J].PLoS One,2013,8(10):e78598.
[27] Callaghan DB,Rogic S,Tan PPC,et al.Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort[J].Clin Genet,2019,96(3):199-206.
[28] Ferron L,Novazzi CG,Pilch KS,et al.FMRP regulates presynaptic localization of neuronal voltage gated calcium channels[J].Neurobiol Dis,2020,138:104779.
[29] Tong XJ,Lopez-Soto EJ,Li L,et al.Retrograde synaptic inhibition is mediated by alpha-neurexin binding to the alpha2delta subunits of N-type calcium Channels[J].Neuron,2017,95(2):326-340.
[30] Frugere L,Duwime C,Malan V,et al.Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder[J].Mol Autism,2019,10:33.
[31] Takata A,Ionita-Laza I,Gogos JA,et al.De novo synonymous mutations in regulatory elements contribute to the genetic etiology of autism and schizophrenia[J].Neuron,2016,89(5):940-947.
[32] Kubota M,Murakoshi T,Saegusa H,et al.Intact LTP and fear memory but impaired spatial memory in mice lacking Ca(v)2.3(alpha(IE)) channel[J].Biochem Biophys Res Commun,2001,282(1):242-248.
[33] Kim JW,Oh HA,Lee SH,et al.T-type calcium channels are required to maintain viability of neural progenitor cells[J].Biomol Ther(Seoul),2018,26(5):439-445.
[34] Talley EM,Cribbs LL,Lee JH,et al.Differential distribution of three members of a gene family encoding low voltage-activated(T-type) calcium channels[J].J Neurosci,1999,19(6):1895-1911.
[35] Splawski I,Yoo DS,Stotz SC,et al.CACNA1H mutations in autism spectrum disorders[J].J Biol Chem,2006,281(31):22085-22091.
[36] Takata A,Miyake N,Tsurusaki Y,et al.Integrative analyses of de novo mutations provide deeper biological insights into autism spectrum disorder[J].Cell Rep,2018,22(3):734-747.
[37] Long S,Zhou H,Li S,et al.The clinical and genetic features of co-occurring epilepsy and autism spectrum disorder in chinese children[J].Front Neurol,2019,10(505).
[38] Chourasia N,Osso-Rivera H,Ghosh A,et al.Expanding the phenotypic spectrum of CACNA1H mutations[J].Pediatr Neurol,2019,93:50-55.
[39] Gangarossa G,Laffray S,Bourinet E,et al.T-type calcium channel Cav3.2 deficient mice show elevated anxiety,impaired memory and reduced sensitivity to psychostimulants[J].Front Behav Neurosci,2014,8:92.
[40] Huang IY,Hsu YL,Chen CC,et al.excavatolide-b enhances contextual memory retrieval via repressing the delayed rectifier potassium current in the hippocampus[J].Mar Drugs,2018,16(11):E405.
[41] D'gama AM,Pochareddy S,Li M,et al.Targeted DNA sequencing from autism spectrum disorder brains implicates multiple genetic mechanisms[J].Neuron,2015,88(5):910-917.
[42] Iossifov I,Ronemus M,Levy D,et al.De novo gene disruptions in children on the autistic spectrum[J].Neuron,2012,74(2):285-299.
[43] Lek M,Karczewski KJ,Minikel EV,et al.Analysis of protein-coding genetic variation in 60706 humans[J].Nature,2016,536(7616):285-291.
[44] De Rubeis S,He X,Goldberg AP,et al.Synaptic,transcriptional and chromatin genes disrupted in autism[J].Nature,2014,515(7526):209-215.

基金

国家自然科学基金(31660289);江西省杰出青年人才资助计划(20171BCB23091);南昌大学研究生创新专项资金项目(CX2018166)

PDF(465 KB)

Accesses

Citation

Detail

段落导航
相关文章

/