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1、DelD631：多发性内分泌腺瘤病2A型RET原癌基因的一个新突变?1962?2007年7月24Et第87卷第28期NatlMed:!丝::!:DelD631:多发性内分泌腺瘤病2A型RET原癌基因的一个新突变姚斌柳学董婷婷陈雄黄知敏翁建平【摘要】目的检测一个多发性内分泌腺瘤病2A型(MEN2A)家系中RET原癌基因突变情况,以探寻该家系发病的分子机制.方法一个MEN2A家系,包括先证者两代人共22位成员的大家系.提取该家系22位成员外周血基因组DNA,扩增先证者RET原癌基因的外显子10,11,进而对纯化后的
2、PCR产物直接测序,并进一步进行克隆测序,判定变异的位点及编码氨基酸序列的变化,测得突变所在的外显子后,将其余几例患者及其亲属相应外显子的扩增产物进行测序.结果4例MEN2A患者均存在D631密码子(GAC)的杂合缺失,碱基序列由TGCGACGAGCTG变为TGCGAGCTG,导致代表天冬氨酸的D631的缺失,即delD631;4例患者中Ⅱ6的一级亲属(Ⅲ10)为该基因突变携带者.克隆测序发现的突变点与Cariff医学遗传学院人类基因突变数据库收录的MEN2A相关的RET原癌基因突变比较,确定为新突变点.结论本
3、研究MEN2A家系存在外显子11的D631杂合缺失突变,是国内外报道的首个RET原癌基因D631缺失突变.临床表现特点:相对于半胱氨酸位点突变,其发病年龄迟,肾上腺嗜铬细胞瘤可早于甲状腺髓样癌发生.【关键词】多内分泌腺瘤形成2a型;点突变;RET原癌基因DelD631:anovelmutationoftheRETproto?oncogeneinmultipleendocrineneoplasiatype2A(MEN2A)0Bin,Xue,DONGn一ting,CHENXiong,小/ⅣG—rain,WENGJi
4、an-ping.'DepartmentofEndocrinology,FirstAffilicatedHospitalofSunYat—SenUniversity,Guangzhou510080,ChinaCorrespondingauthor:WENGJian-ping,Email:gzweng]p@pub.guangzhou.gd.ca【Abstract】ObjectiveTodetectRETmutationsinarareChinesebigfamilywithMultipleendocrineneop
5、lasiatype2A(MEN2A).MethodsOneMEN2Afamily,includingtheproband.have22membersoftwogenerations.itisararebigfamilyinmodernChinesefamilies.TheDNAsofthe22membersfromthefamilyincluding4patientswereextractedfrombloodleukocytes,PCRandgenesequencingofPCRproductsbyanaut
6、omatedDNAsequencerwereappliedtoscantheexonl0and11ofRETproto—oncogene.SequencingresultswerecomparedwiththePubmeds.Clonesequencingwasadopttofurtherconfirmtheresults,thenverifyingthenovelmutationthroughthehumangenemutationdatabaseattheinstituteofmedicalgenetics
7、incardiff.Invitrogenbiotechnologycompany(Shanghai)providedthetechnologyofclonesequencing.ResultsAnoveldeletionmutationofD631(GAC)(delD631)wasdetectedinexonl1oftheIu玎proto?oneogenein4MEN2Apatientsofthefamily,thisraredeletionmutationofI)631(GAC)leadbasesequenc
8、eofTGCAGACGAGCTGchangetoTGCGAGCTG.Besides4MEN2Apatients,thesonofII6(thefirstclassrelative)wasfoundtobeacarrierofdelD631mutation.ConclusionAnoveldeletionmutation(delD631)ofRETproto.oncogenewasdet
