进行性家族性肝内胆汁淤积症3型基因突变分析与临床研究.pdf

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1、中华实用儿科临床杂忠2014年4月第29卷第8期ChinJApplClinPediatr，April2【】!0l_!!．·581··遗传代谢内分泌疾病·进行性家族性肝内胆汁淤积症3型基因突变分析与临床研究林瑞珠刘丽盛慧英徐翼李秀珍程静蔡燕娜卢致琨李端张文徐爱晶范莉萍【摘要】目的分析进行性家族性肝1人J月H汁淤积症3型(PFIC3)临床表现、遗传学特点和基冈突变特点。方法应用聚合酶链反廊一直接测序方法对2例临床疑似PFIC3的中国患儿ABCB4基因的27个外显子及侧翼序列进行突变检测，并对其家庭主要成员进行相应突变基凶检测，收集临床资料分析。健康时照组为无血缘关系的健康儿章

2、50例，男27例，女23例，均为汉族。结果2例患儿主要表现为胆汁淤积、黄疸伴瘙痒、肝火，血清一谷氨酰转肽酶、月H汁酸升高例1为ABCB4基c．2489insA和c．．143—3145delGCAinsCC复合杂合突变，例2为c．966G>C(P．G3l9R)和c．3220G>A(P．G1074R)复合杂合突变，均为新发突变；2例患儿父母及例2弟弟均为突变基携带者。结论发现r4种尚未见报道的ABCB4基囚新突变，c．2489insA／(．3143—3145delGCAinsCC突变IJf能与严重临床表相关。【关键词】胆汁淤积；婴儿肝炎综合征；黄疸；ABCB4基因Analys

3、isofclinicandgenemutationonpatientswithprogressivefamilialintrahepaticcholestasistype3LinRuizhu，LiuLi，ShengHuiying，XuYi，LiXiuzhen，Chengring，CaiYanna，LuZhikun，LiDuan，ZhangWen，XuAiring，FanLiping．DepartmentofEndocrinologyandMetabolism，GuangzhouWomenandChildrentsMedicalCenter，GuangzhouMedical

4、University，Guangzhou510623，ChinaCorrespondingauthor：LiuL，Email：filiuxia@hotmail．conl【Abstract】ObjectiveToanalyzetheclinicandgeneticalcharacteristicsofprogressivefamilialintrahepaticcholestasistvpe3(PFIC3)ofinfancycausedbyATPbindingcassettetransporterA4(ABCB4)genenmtation．MethodsClinif。aln

5、tanifestati(msandlaboratorytestresultsofthe2patientsweresummarized．GenomicDNAfromperipheralbloodwascollectedfnrgeneticanalysisinthesepatients．A1lfragmentsofexonsoftheABCB4geneofkeymembersofthe2familieswereamplifiedbypolymerasechainreaction—sequencebasedtypingmethod．Forwardsequencingwasper

6、—formedfi)rmutationanalysis．FiftyunrelatedindividualsinHanpopulationwerehealthycontro1group，male27cases，fe—male23cases．ResultsThe2patientshadpersistentintrahepaticcholestasis，jaundicewithpruritus，hepatomegaly，anda11showedelevatedlevelsofserumgamma—glutamyltranspeptidaseandbileacid．Twopati

7、entshadABCB4genemHtations．whichwerenovelnmtationsneverreposedbefore．Ainse~ionmutationofe．2489insAinexon21combinedwithamutationofc．31433145delGCAinsCCinexon25．whichwasacompoundheterozygousmutation，wasidentifiedinpatientl：Amissensemutationofe．966G>C(P．G319R)inexon9com