核心家系孤独症患儿FOXP1基因的突变及CNV分析
- 杨曹骅1,杜亚松1,刘文文1,张林娜1,王红艳2,公晓红2
作者信息
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Mutation and copy number variation analyses of FOXP1 gene in autistic children of nuclear family.
- YANG Cao-hua1,DU Ya-song1,LIU Wen-wen1,ZHANG Lin-na1,WANG Hong-yan2,GONG Xiao-hong2.
Author information
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文章历史
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摘要
目的 研究转录因子FOXP1在汉族孤独症患儿核心家系中的外显子突变,并进行初步的功能预测。 方法 288例孤独症患儿及生物学父母进行FOXP1外显子区域基因测序和拷贝数变异(copy number variation,CNV)检测;使用POLYPHEN及SIFT等软件进行功能预测。 结果 4例患儿的FOXP1基因外显子区域发现4个错义突变,包括P42S,H53Q,L68R和M590V。在CNV检测中为阴性结果。通过功能预测发现,FOXP1的四个罕见突变可能不会对FOXP1编码蛋白产生重要影响。 结论 汉族人群中,FOXP1基因可能不是孤独症的主要致病基因。
Abstract
Objective To study the transcription factor FOXP1 exon in the Han Chinese children with autism nuclear families,and finish the initial function prediction. Methods The gene sequencing in FOXP1 exon regions of 288 cases of children with autism and their biological parents were conducted to detect the copy number variation (CNV) of FOXP1.The POLYPHEN and SIFT software were used to do the function prediction. Results In 4 patients,four missense mutations were found in FOXP1 exon region,P42S,H53Q,L68R,and M590V.And there were the negative results in the detection of copy number variation.After the function prediction,the four rare mutations might not have an important impact on the protein. Conclusion In the Han Chinese population,the FOXP1 gene may not be one of the important autism disease-causing genes.
关键词
孤独症 / 核心家系 / FOXP1 / 基因测序 / 拷贝数变异
Key words
autism / nuclear families / FOXP1 / gene sequencing / copy number variation
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参考文献
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[16] Bowers JM,Konopka G.The role of the FOXP family of transcription factors in ASD[J].Dis Markers,2012,33(5):251-260.
[17] Pariani MJ,Spencer A,Graham JM,et al.A 785kb deletion of 3p14.1p13,including the FOXP1 gene,associated with speech delay,contractures,hypertonia and blepharophimosis[J].Eur J Med Genet,2009,52(2-3):123-127.
[18] O'Roak BJ,Deriziotis P,Lee C,et al.Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations[J].Nat Genet,2011,43(6):585-589.
[2] Clifford SM,Hudry K,Elsabbagh M,et al.Temperament in the first 2 years of life in infants at high-risk for autism spectrum disorders[J].J Autism Dev Disord,2013,43(3):673-686.
[3] Barger BD,Campbell JM,McDonough JD,Prevalence and onset of regression within autism spectrum disorders:a meta-analytic review[J].J Autism Dev Disord,2013,43(4):817-828.
[4] Autism I,Developmental Disabilities Monitoring Network Surveillance Year Principal,C.Centers for Disease,et al.Prevalence of autism spectrum disorders-autism and developmental disabilities monitoring network,14 sites,United States,2008[J].MMWR Surveill Summ,2012,61(3):1-19.
[5] Lundstrom,Chang SZ,Rastam M,et al.Autism spectrum disorders and autistic like traits:similar etiology in the extreme end and the normal variation[J].Arch Gen Psychiatry,2012,69(1):46-52.
[6] Yang Y,Pan C.Role of metabotropic glutamate receptor 7 in autism spectrum disorders: a pilot study[J].Life Sci,2013,92(2):149-153.
[7] Michaelson JJ,Shi Y,Gujral M,et al.Whole-genome sequencing in autism identifies hot spots for de novo germline mutation[J].Cell,2012,151(7):1431-1442.
[8] Ferland RJ,Cherry TJ,Preware PO,et al.Characterization of Foxp2 and Foxp1 mRNA and protein in the developing and mature brain[J].J Comp Neurol,2003,460(2):266-279.
[9] Shu W,Yang H,Zhang L,et al.Characterization of a new subfamily of winged-helix/forkhead (Fox) genes that are expressed in the lung and act as transcriptional repressors[J].J Biol Chem,2001,276(29):27488-27497.
[10] Hamdan FF,Daoud H,Rochefort D,et al.De novo mutations in FOXP1 in cases with intellectual disability,autism,and language impairment[J].Am J Hum Genet,2010,87(5):671-678.
[11] Anitha A,Thanseem I,Nakamura K,et al.Protocadherin alpha (PCDHA) as a novel susceptibility gene for autism[J].J Psychiatry Neurosci,2013,38(3):192-198.
[12] Krug DA,Arick J,Almond P.Behavior checklist for identifying severely handicapped individuals with high levels of autistic behavior[J].J Child Psychol Psychiatry,1980,21(3):221-229.
[13] Toma C,Hervas A,Torrico B,et al.Analysis of two language-related genes in autism: a case-control association study of FOXP2 and CNTNAP2[J].Psychiatr Genet,2013,23(2):82-85.
[14] Teramitsu I,Kudo LC,London SE,et al.Parallel FoxP1 and FoxP2 expression in songbird and human brain predicts functional interaction[J].J Neurosci,2004,24(13):3152-3163.
[15] Bacon C,Rappold GA.The distinct and overlapping phenotypic spectra of FOXP1 and FOXP2 in cognitive disorders[J].Hum Genet,2012,131(11):1687-1698.
[16] Bowers JM,Konopka G.The role of the FOXP family of transcription factors in ASD[J].Dis Markers,2012,33(5):251-260.
[17] Pariani MJ,Spencer A,Graham JM,et al.A 785kb deletion of 3p14.1p13,including the FOXP1 gene,associated with speech delay,contractures,hypertonia and blepharophimosis[J].Eur J Med Genet,2009,52(2-3):123-127.
[18] O'Roak BJ,Deriziotis P,Lee C,et al.Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations[J].Nat Genet,2011,43(6):585-589.
基金
国家重点基础研究发展计划(973)(2010CB529602);上海市科委重点项目(11411952401);上海市新三年计划项目(GWIII-32);上海市家庭文明建设重点立项课题(2012)
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