上海医学2010年第33卷第12期PraderWilli综合征·论著。四例报道(附临床及遗传学诊断)张豫文洪洁贾慧英戈岩李小英宁光【摘要】目的观察并分析4例Prader—Willi综合征(PWS)患者的临床特征及分子遗传基础。方法应用甲基化特异性聚合酶链反应(MSPCR)以及荧光原位杂交(FISH)技术对4例临床诊断为PWS的患者进行sNR尸N基因的分析研究。结果3例患者MSPCR结果均提示缺乏父源的相关片段，而仅母源DNA，即第15号染色体母源单亲二体(matUPD15)，FISH检测提示该3例患者sNR_PN基因片段不存在微小缺失。另l例患者MS-PCR结果正常；但FISH检测发现1个不平衡移位46，XX，t(7；15)。结论父源15qll一13特异区带缺失及matUPD15亦与我国PWS患者致病的分子病理缺陷有关。临床开展相关的细胞分子遗传学实验诊断对PWS的临床诊断以及分子遗传基础的分析都具有积极的作用。【关键词】Prader—Willi综合征；sNRPN基因；基因印记；单亲二体性；甲基化特异性聚合酶链反应；荧光原位杂交Prader．wiIIisyndrome：aclinicalandepigeneticstudyof4casesZHANGYuwen，HONGJie，JIAHuiying，GEYen，LIXiaoying，NINGGuangShanghaiClinicalCenterforEndocrineandMetabolicDiseases，ShanghaiInstituteofEndocrineandMetabolicDiseases，RuqinHospital，ShanghaiJiaotongUniversitySchoolofMedicine，Shanghai200025，ChinaCorrespondingauthor：HONGJieE-mail：hongjie13d@hotmail．cam[Abstract]ObjectiveTostudythemoleculargeneticdefectsandgenomicimprintingbasisofChinesePrader．Willisyndrome(PWS)patientsandtoevaluatetheclinicalapplicationsofadiferentialdiagnostictestforPWSMethodsFluorescenceinsituhydbridiezatiOn(FISH)andmethylation—specificpolymerasechainreaction(MS．PCR)techniaueswereappliedfor4clinicallysuspectedPWSpatientsUsingS^『只P～probeforidentifyingthecriticallocusinthePWSregion，D15Z1andPMLcontrolprobesforidentifying5parmand15qarm，wedetectedthedeletionsof15ainPWSMS．PCRwasperformedusingtheCpGenomePrader—Willi／AngelmanAmplificationKitofChemicon(Temecula，CA，USA)．PCRproductswereobtainedusingeithertheMorthePprimersets(GenBankaccessionNo．L32702)afterthebisulfitemodificationofgenomicDNAResuItsAfterhybridizationwithmixedprobes．onepatientwasfoundtohaveanunbalanceddenovotranslocation46，XX，t(7；15)，whileMS—PCRwasnormalBisulfite—modifiedDNAfr0mtheother3PWSpatientsamplifiedwithmethylatedallele-specificprimerpairshowedonlymaternal131bpPCRproducts，indicatingthematernaluniparentaldisomy(UPD15)ConclusionGenomicimprintingplaysanimportantroleinthemolecularpathogenesisofPWScausedbypaternaImicrodeletionsof15a11—13ormaternalUPDofchromosome15ThebasicdefectseemstobeanabsentfunctionofPWSgenesthatarenormallyexpressedonlyfromthepaternalchromosome15MS—PCRisareliablediagnosismethodforPWSpatientswhoshowabnormalmethylationatSNRPN．ThegeneticdiferentialtestsforPWSareimportantindeterminingfamilialrecurrencerisk．(ShanghaiMedJ，2010，33：1123—1128)[Keywords]Prader—Willisyndrome；SNRP～gene；Geneimprinting；Uniparentaldisomy；Methylation—specificpolymerasechainreaction；Fluorescenceinsituhydbrezati0n作者单位：200025上海交通大学医学院附属瑞金医院内分泌代谢科，上海市内分泌代谢病f临床中心，上海市内分泌代谢病研究所通信作者：洪洁，电子邮箱为hongjiel3d@hotmai]．corllPrader—Willi综合征(PWS)又称为肌张力低下智能障碍性腺发育滞后一肥胖综合征，是导致人类肥胖的最常见遗传性的综合征之一。临床表现主要影响中枢神经系统，特别是下丘脑的畸形综合征。其基本特征为：胎动减少，肥胖，肌张力减退，智力障碍，身材矮小，促性腺激素分泌不足导致的性腺机能减退和手足小，多见于男性，出E时体重较正常人轻[2一。其明确诊断需根据Holm及Cassidy等于1993年所提出的诊断...
