家族性小瞼裂綜合征文章

2家族性小瞼裂綜合征致病候選基因的相關(guān)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家族性小瞼裂綜合征致病候選基因的相關(guān)研究小瞼裂綜合征又稱瞼裂狹小-上瞼下垂-逆向型內(nèi)眥贅皮綜合征（BPES是 6了從基因型到表型的研究。DeBaere[10-11]等為了研究基因型-表型的相關(guān)性，收BPES；另外突變能夠?qū)е露嗑郾彼峤Y(jié)構(gòu)呈現(xiàn)一個(gè)延長的趨勢(shì)，主要表現(xiàn)為II型BPES；但如果發(fā)生的突變能夠?qū)е骂A(yù)測(cè)蛋白包含完整的叉頭結(jié)構(gòu)域和多聚丙酶鏈反應(yīng)、Sanger測(cè)序等技術(shù)，定位克隆致病基因或者對(duì)可疑染色體區(qū)域進(jìn)行成本更低、范圍更全。目前全外顯子組測(cè)序技術(shù)（WES）已經(jīng)成為DNA測(cè)7組的1%左右，但是其包含蛋白質(zhì)合成所需的絕大部分信息，因此外顯子是人類基因不可或缺的重要組成部分。85%左右的人類基因疾病都可能與這些編碼序列全外顯子組測(cè)序技術(shù)的應(yīng)用進(jìn)一步加快了學(xué)者們對(duì)一些罕見性遺傳病致病8針對(duì)先天性小瞼裂綜合征的患者在進(jìn)行手術(shù)治療的時(shí)候我們要對(duì)目前普遍聯(lián)合筋膜鞘懸吊術(shù)比額肌瓣懸吊術(shù)要更好一些,除此之外，聯(lián)合筋膜鞘懸吊術(shù)還9Qubit儀、凝膠成像系統(tǒng)、熒光實(shí)時(shí)定量PCR儀所用設(shè)備：高通量測(cè)序系統(tǒng)IlluminaNextsTerminatorv1.1&v3.15XSequencingBuffer、Hi-DiFo明書(MyGenostics，Inc.Beijing，連接到3'端進(jìn)行末端修復(fù)，然后與lllu品在此過程中用一個(gè)唯一的索引標(biāo)記)，并使用安捷倫生物分析儀進(jìn)行檢測(cè)。選根據(jù)下表所示添加各組分，其中10×FragmentationBuffer和5×WGS體積(μl）5X11234體積(μl）825體積(μl）111在200-500bp左右得到清晰略彌散的條帶，則為建庫成功。液與上述緩沖液進(jìn)行混合，然后將其轉(zhuǎn)移到80ESP6500、dbSNP、EXAC、HGMD)關(guān)聯(lián)，并使用REVEL、SIFT、PolyPhen-2、號(hào)外顯子上游36bp，采用Sanger測(cè)序方法對(duì)先證者及其家系成員gDNA進(jìn)行驗(yàn)c.672_701dupAGCGGCTGCAGCAGCTGCGGCTGCAGCCGC雜合突變，導(dǎo)致氨基酸發(fā)生整PS4：ClinVar數(shù)據(jù)庫已有對(duì)該位點(diǎn)c.672_701dupAGCGGCTGCAGCAGCTGCGGCTGCAGCCGC雜合突變，而其他正常成員均A225_A234dupAAAAAAAA 內(nèi)，它會(huì)使多聚丙氨酸鏈發(fā)生延長，有學(xué)者認(rèn)為該結(jié)構(gòu)的延長會(huì)影響所編碼的雙孔鉀離子通道以及退行性蛋白。有學(xué)者通過小鼠神經(jīng)瘤母細(xì)胞篩選鑒定出蛋白主要是在三叉神經(jīng)的感覺細(xì)胞中分布，另外在被根神經(jīng)節(jié)細(xì)胞、Merkel細(xì)蛋白質(zhì)結(jié)構(gòu)變化對(duì)于相關(guān)遺傳性疾病的發(fā)生和發(fā)展具有Gordon綜合征(GS)在臨床中是并不多見的疾病，其作為一種常染色體顯性例是存在相同錯(cuò)義突變現(xiàn)象的，這種錯(cuò)義突變都表現(xiàn)為c.8057G>A(p.Arg2686His)，而腭裂的發(fā)生正好與該疾病之間存在很大的聯(lián)系，所以可以初步認(rèn)為022068.3：c.8181_8183de果為有害。根據(jù)ACMG分類，該變異滿足PS2、PM2、PP3、PP4評(píng)分，因此被解端。這些突變?cè)诓煌潭壬鲜筆iezo2蛋白的二級(jí)結(jié)構(gòu)形態(tài)發(fā)生改變，或者使的mRNA，必須經(jīng)過內(nèi)含子的去除以及相鄰?fù)怙@子的連接，我們將這一過程稱為mRNA的剪接，它是真核細(xì)胞基因表達(dá)中非常重要的一個(gè)生物過程，也是蛋白質(zhì)分子多樣性產(chǎn)生的關(guān)鍵機(jī)制之一，其中mRNA在了重要的作用。我們將外顯子和內(nèi)含子兩者之間的交界處稱為剪接位點(diǎn)，前體除，然后規(guī)范地將外顯子連接形成成熟的mRNA，在這種情況下拼接的改變是非SR蛋白家族主要與剪接增強(qiáng)子結(jié)合，發(fā)揮促進(jìn)剪接位點(diǎn)識(shí)別和促進(jìn)剪接過程的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,Do?anMDM,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,陳濤,趙穎.先天[17]張玉琴,盛翠華.聯(lián)合筋膜鞘懸吊術(shù)治[18]趙英年,葛洪剛,沈清俐.聯(lián)合筋膜鞘懸吊術(shù)和[20]ZhangL,Wangationoftheforkheadtranscriptionalfactor2(FOXL2)genemutationsinfourChifamilieswithblepharophimosissyndrome.MolVis.2013NoD:24265544;PMCID:PMC3834601.RA.ThemutationsandpotentialtargetsoftheforkheadtranscriptionfactorFOXL2.MolCellEndocrinol.2008Jan30;282(1-2):2- 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