CAJ | 학술논문

目的对4例马凡综合征(Marfan syndrome,MFS)患者进行原纤维蛋白-1基因(fibrillin-1,FBN1突变检测及产前诊断,为患者提供病因诊断和遗传咨询.方法应用PCR扩增和DNA测序对4例典型的MFS患者进行FBN1基因筛查.确定突变类型后,于孕18～20周穿刺抽取羊水,抽提DNA,PCR扩增FNB1基因,对PCR产物进行双向测序.结果例1 FBN1基因第46内含子的+1位碱基发生置换(IVS46+1G＞ A)；例2第35外显子的4453位碱基发生错义突变c.4453T＞G(Cys1485Gly)；例3第21外显子2585位碱基发生错义突变巴2585G＞A(Cys862Tyr)；例4第28外显子3536位碱基A缺失c.3536 delA.c.4453T＞G(Cys1485Gly)、c.2585G＞A(Cys862Tyr)和c.3536 delA为新突变.4例胎儿羊水的标本也分别检测到IVS46+1G＞A、c.4453T＞G(Cys1485Gly)、c.2585G＞A(Cys862Tyr)和c.3536 delA突变.结论 FBN1基因筛查可以检测出患者及其家系中胎儿的突变位点和类型,具有明确的诊断价值,有助于遗传咨询.
목적 대4례마범종합정(Marfan syndrome,MFS)환자진행원섬유단백-1기인(fibrillin-1,FBN1돌변검측급산전진단,위환자제공병인진단화유전자순.방법 응용PCR확증화DNA측서대4례전형적MFS환자진행FBN1기인사사.학정돌변류형후,우잉18～20주천자추취양수,추제DNA,PCR확증FNB1기인,대PCR산물진행쌍향측서.결과 례1 FBN1기인제46내함자적+1위감기발생치환(IVS46+1G＞ A)；례2제35외현자적4453위감기발생착의돌변c.4453T＞G(Cys1485Gly)；례3제21외현자2585위감기발생착의돌변파2585G＞A(Cys862Tyr)；례4제28외현자3536위감기A결실c.3536 delA.c.4453T＞G(Cys1485Gly)、c.2585G＞A(Cys862Tyr)화c.3536 delA위신돌변.4례태인양수적표본야분별검측도IVS46+1G＞A、c.4453T＞G(Cys1485Gly)、c.2585G＞A(Cys862Tyr)화c.3536 delA돌변.결론 FBN1기인사사가이검측출환자급기가계중태인적돌변위점화류형,구유명학적진단개치,유조우유전자순.
Objective To screen for mutations of fibrillin-1 (FBN1)gene in 4 patients with Marfan syndrome in order to provide prenatal diagnosis and genetic counseling.Methods Potential mutations of the FBN1 gene in the probands were detected with PCR and DNA sequencing.Subsequently,genomic DNA was extracted from amniotic fluid obtained between 18 to 20 weeks gestation.The mutations were confirmed with denaturing high-performance liquid chromatography robust microsatellite instability (DHPLC-MSI)analysis with maternal DNA as reference.The products were further analyzed by direct sequencing and BLAST search of NCBI database.Results An IVS46+1G＞A substitution was identified in patient A at +1 position of intron 46 of the FBN1 gene.Two novel missense mutations (c.4453T＞G,Cys1485Gly)were respectively discovered at positions +4453 of intron 35 in patient B and position +2585 of intron 21 in patient C.In patient D,a novel deletion (c.3536 delA) was found at position +3536 of intron 28.In all of the 4 cases,the same mutations have been identified in the fetuses.Conclsion FBN1 gene analysis can provide accurate diagnosis of Marfan syndrome for both probands and fetuses,which will facilitate both prenatal diagnosis and genetic counseling.