家族性小睑裂综合征文章

2家族性小睑裂综合征致病候选基因的相关研究3blepharophimosis-ptosis-epicanthblepharophimosis-ptosis-epicantTheSecondPeople'sHospitalofYunnanProvincewresultswerescreenedforcandidatepathogenicgenesites.TheresultswereverifiedAmong5membersinFamily1,3werepatientsin3generations,whichwasconsistentwithautosomaldominantgeneticheredity.G>Cmutationat36bpupstreamofExon11inPIEZO2genewasfoundafterwhole-exomesequencing.Sangersequencingconfirmedthattheother2patientsinthefamilycarriedthesamemutation,butthemutationwasnotdetectedinnormalmembersofthefamily.BothFamily2andFamily3carriedreportedmutationsinFOXL2gene.Among4membersinFamily2,2werepatientscarriedaheterozygousmutationofFOXL2gene1,whichwasamissensemutation05H).InFamily3,3outof5memberswerepatientsandtheycarriedacompletecodemutationc.672_701dupAGCGGCTGCAGCAGCTGCGGCTGCAGCCGC(p.A225_A234dupAAAAAAAAAA).ecausesofblepharophimosis-ptosis-epicanthus-inversussyndromein2families,4whichprovidesatheoreticalbasisforgeneticcounselingandfertility.Atthesametime,themutationofPIEZO2geneisanovelmutation,whichisanimportantriskfactorfortheoccurrenceofblepharophimosis-ptosis-epicanthus-inversussyndromeinFamily2,anditisapossiblepathogenicgenemutationinthispedigree.Furtherstudycannotonlybroadenthegenemutationspectrumofsmalleyelidfissuresyndrome,butalsohelptodeepentheunderstandingofthepathogenesisofblepharophimosis-ptosis-epicanthus-inversussyndrome.sequencing;FOXL2g5家族性小睑裂综合征致病候选基因的相关研究小睑裂综合征又称睑裂狭小-上睑下垂-逆向型内眦赘皮综合征（BPES是 6了从基因型到表型的研究。DeBaere[10-11]等为了研究基因型-表型的相关性，收BPES；另外突变能够导致多聚丙氨酸结构呈现一个延长的趋势，主要表现为II型BPES；但如果发生的突变能够导致预测蛋白包含完整的叉头结构域和多聚丙酶链反应、Sanger测序等技术，定位克隆致病基因或者对可疑染色体区域进行成本更低、范围更全。目前全外显子组测序技术（WES）已经成为DNA测7组的1%左右，但是其包含蛋白质合成所需的绝大部分信息，因此外显子是人类基因不可或缺的重要组成部分。85%左右的人类基因疾病都可能与这些编码序列全外显子组测序技术的应用进一步加快了学者们对一些罕见性遗传病致病8针对先天性小睑裂综合征的患者在进行手术治疗的时候我们要对目前普遍联合筋膜鞘悬吊术比额肌瓣悬吊术要更好一些,除此之外，联合筋膜鞘悬吊术还9Qubit仪、凝胶成像系统、荧光实时定量PCR仪所用设备：高通量测序系统IlluminaNextsTerminatorv1.1&v3.15XSequencingBuffer、Hi-DiFo明书(MyGenostics，Inc.Beijing，连接到3'端进行末端修复，然后与lllu品在此过程中用一个唯一的索引标记)，并使用安捷伦生物分析仪进行检测。选根据下表所示添加各组分，其中10×FragmentationBuffer和5×WGS体积(μl）5X11234体积(μl）825体积(μl）111在200-500bp左右得到清晰略弥散的条带，则为建库成功。液与上述缓冲液进行混合，然后将其转移到80ESP6500、dbSNP、EXAC、HGMD)关联，并使用REVEL、SIFT、PolyPhen-2、号外显子上游36bp，采用Sanger测序方法对先证者及其家系成员gDNA进行验c.672_701dupAGCGGCTGCAGCAGCTGCGGCTGCAGCCGC杂合突变，导致氨基酸发生整PS4：ClinVar数据库已有对该位点c.672_701dupAGCGGCTGCAGCAGCTGCGGCTGCAGCCGC杂合突变，而其他正常成员均A225_A234dupAAAAAAAA 内，它会使多聚丙氨酸链发生延长，有学者认为该结构的延长会影响所编码的双孔钾离子通道以及退行性蛋白。有学者通过小鼠神经瘤母细胞筛选鉴定出蛋白主要是在三叉神经的感觉细胞中分布，另外在被根神经节细胞、Merkel细蛋白质结构变化对于相关遗传性疾病的发生和发展具有Gordon综合征(GS)在临床中是并不多见的疾病，其作为一种常染色体显性例是存在相同错义突变现象的，这种错义突变都表现为c.8057G>A(p.Arg2686His)，而腭裂的发生正好与该疾病之间存在很大的联系，所以可以初步认为022068.3：c.8181_8183de果为有害。根据ACMG分类，该变异满足PS2、PM2、PP3、PP4评分，因此被解端。这些突变在不同程度上使Piezo2蛋白的二级结构形态发生改变，或者使的mRNA，必须经过内含子的去除以及相邻外显子的连接，我们将这一过程称为mRNA的剪接，它是真核细胞基因表达中非常重要的一个生物过程，也是蛋白质分子多样性产生的关键机制之一，其中mRNA在了重要的作用。我们将外显子和内含子两者之间的交界处称为剪接位点，前体除，然后规范地将外显子连接形成成熟的mRNA，在这种情况下拼接的改变是非SR蛋白家族主要与剪接增强子结合，发挥促进剪接位点识别和促进剪接过程的GL,GanaS,CaligoMA,BertelloniS.Blepharophimosis,Ptosis,EpicanthSyndrome:NewReportwitha197-kbDeletionUpstreamofFOXL2andReviewoftheLiterature.MolSyndromol.2019May;10(3):147-153.[2]VerdinH,DeBaereE.BlepLJH,GrippKW,MirzaaGM,(WA):UniversityofWashington,S[3]KabaMDS,DoğanMDM,BulanMDK,MDMD,KocamanMDS.Blepharophimosis,Ptosis,andEpicrome:ExpandingthePhenotype.CleftPalateCraniofacJ.2016Nov;53(6):732-735.hCongenitalHypothyroidismandBrachydactylyistReconstrSurg.2017May/Jun;33(3SSupps,ptosis,andepicanthusinversussyndrome(BPES)associatedofband3q22:reviewandgeneassignmenttotheinterfaceofband3q22.3and3q2[6]CrisponiL,DeianaM,agarajaR,PorcuS,RistaldiMS,MarzellaR,RocchiM,NicolinoM,Lienhardt-RouieA,NivelonA,VerloesA,SchlG.TheputativeforkheadtranscriptionfactorFOXL2ismutatedinblephatosis/epicanthusinversussyndrome.NatGenet.2001Feb;27(2):159-66.Q.NovelFOXL2mutationscauseblepharophimosis-ptosis-epicanthusinversussyndromewithprematureovarianinsufficiency.MolGenetGenomicMed.[8]BeysenD,DePaepeA,DeBaereE.FOXL2mutationsandgenomicnBPES.HumMutat.2009Feb;30(2):158-69.[9]CaburetS,GeocriptionfactorFOXL2:atthecrossroadsofovarianphysiologyandellEndocrinol.2012Jun5;356(1-2):55mofFOXL2genemutationsinblepharophimosis-ptosis-epicanthusinversus(BPES)familiesdemonstratesagenotype--phenotypecorrelation.HumMo0(15):1591-600.MeireF,PlompAandBPES:mutationalhotspots,phenotypicvariability,andrevisionofthegenotype-phenotypecorrelation.AmJHumGenet.2003Feb;72(2):gM,BhattacharjeeA,EichlerEE,BamshadM,NickersonDA,captureandmassivelyparallelsequencingo[13]ChawlaB,BhadaraM,GhoseS.Clinical,radiologic,andgeneticfeaturesinblepharophimosiandepicanthusinversussyndromeintheIndiani.2013Apr26;54(4):2985-91.tcomestudyofthreedifferenttechniques.JPlastReconstrAesthetSurg.2015Oct;68(10):1346-51.[16]李爽,李冬梅,艾立坤,陈涛,赵颖.先天[17]张玉琴,盛翠华.联合筋膜鞘悬吊术治[18]赵英年,葛洪刚,沈清俐.联合筋膜鞘悬吊术和[20]ZhangL,Wangationoftheforkheadtranscriptionalfactor2(FOXL2)genemutationsinfourChifamilieswithblepharophimosissyndrome.MolVis.2013NoD:24265544;PMCID:PMC3834601.RA.ThemutationsandpotentialtargetsoftheforkheadtranscriptionfactorFOXL2.MolCellEndocrinol.2008Jan30;282(1-2):2- 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