CAJ | 학술논문

目的研究胎儿短肢畸形的致病基因突变位点. 方法 2008年8月至2011年8月,妊娠18～24周和(或)30～32周常规胎儿超声检查发现胎儿肢体明显短小者共10例,知情同意后引产终止妊娠,同时抽取羊水或脐带血进行胎儿染色体核型分析.采用聚合酶链反应及直接测序技术检测羊水或脐带血成纤维细胞生长因子受体3(fibroblast growth factor receptor 3,FGFR3)基因的热点突变位点.染色体及FGFR3基因检测异常胎儿的双亲进行FGFR3基因相同部位的测序.1例胎儿(病例3)颅骨骨化差,考虑软骨生成不全,进行FGFR3基因全部外显子及SLC26A2,Trip11基因外显子测序. 结果 10例短肢畸形胎儿,妊娠中、晚期各检出5例,均引产终止妊娠.染色体核型分析发现1例为嵌合体(46,XY/45,XY,-18),余9例正常.10例胎儿全部进行了FGFR3基因热点突变部位的检测,发现4例基因突变.其中1例为罕见的c.1108G＞T(G370C)突变,胎龄21+3周,诊断致死性骨发育不良;另3例胎龄30～32周胎儿为FGFR3 c.1138G＞A(G380R)突变,明确诊断为软骨发育不全.4例基因突变胎儿的双亲均未见相同位点突变,再发风险低,其中3例胎儿母亲目前已再次妊娠分娩,新生儿无异常.病例3胎儿FGFR3基因全部外显子及SLC26A2,Trip11基因检测均未发现致病突变. 结论染色体及FGFR3基因热点突变部位的检测可为部分短肢畸形胎儿明确致畸原因,为患病家庭提供准确的遗传咨询及再次妊娠的产前诊断;妊娠晚期超声发现胎儿肢体明显短小,应考虑软骨发育不全.
목적 연구태인단지기형적치병기인돌변위점. 방법 2008년8월지2011년8월,임신18～24주화(혹)30～32주상규태인초성검사발현태인지체명현단소자공10례,지정동의후인산종지임신,동시추취양수혹제대혈진행태인염색체핵형분석.채용취합매련반응급직접측서기술검측양수혹제대혈성섬유세포생장인자수체3(fibroblast growth factor receptor 3,FGFR3)기인적열점돌변위점.염색체급FGFR3기인검측이상태인적쌍친진행FGFR3기인상동부위적측서.1례태인(병례3)로골골화차,고필연골생성불전,진행FGFR3기인전부외현자급SLC26A2,Trip11기인외현자측서. 결과 10례단지기형태인,임신중、만기각검출5례,균인산종지임신.염색체핵형분석발현1례위감합체(46,XY/45,XY,-18),여9례정상.10례태인전부진행료FGFR3기인열점돌변부위적검측,발현4례기인돌변.기중1례위한견적c.1108G＞T(G370C)돌변,태령21+3주,진단치사성골발육불량;령3례태령30～32주태인위FGFR3 c.1138G＞A(G380R)돌변,명학진단위연골발육불전.4례기인돌변태인적쌍친균미견상동위점돌변,재발풍험저,기중3례태인모친목전이재차임신분면,신생인무이상.병례3태인FGFR3기인전부외현자급SLC26A2,Trip11기인검측균미발현치병돌변. 결론 염색체급FGFR3기인열점돌변부위적검측가위부분단지기형태인명학치기원인,위환병가정제공준학적유전자순급재차임신적산전진단;임신만기초성발현태인지체명현단소,응고필연골발육불전.
Objective To identify the genetic mechanism of fetuses with short limbs deformity.Methods From Aug.2008 to Aug.2011,ten fetuses with obvious short limbs were found in ultrasound screening performed at 18-24 and (or) 30-32 gestational weeks and underwent artificial induced labor with the patient' consent.Amniotic fluid or cord blood of the fetuses was collected for karyotyping analysis and detection of mutation point of fibroblast growth factor receptor 3 (FGFR3)gene by polymerase chain reaction and gene sequencing.One fetus (case 3) who presented with achondrogenesis underwent sequencing of SLC26A2 and Trip11 gene meanwhile.Results Among the 10 fetuses with short limbs deformity,five cases were found during second trimester and five during third trimester.Nine cases were identified as normal karyotype and one was chimera (46,XY/45,XY,- 18).One fetus carried a rare FGFR3 mutation of c.1108G＞T (G370C) and was diagnosed as thanatophoric dysplasia at 21+3 weeks.Three fetus carried c.1138G＞A (G380R) mutation and were diagnosed as achondroplasia.These four families had low recurrent risk because no gene mutations were found in the parents.Three mothers of these four fetuses were pregnant again and had normal neonates now.No mutations were found in all gene sequencing in case 3.Conclusions Karyotyping analysis and sequencing of FGFR3 gene could find causative gene mutations and provide genetic counselling and prenatal diagnosis for some fetuses with short limbs deformity.In the third trimester,achondroplasia is the most possible diagnosis when short limbs fetus is found by ultrasound.