马凡综合征两种新的原纤维蛋白-1基因突变

Two novel mutations in fibrillin-1 gene of Marfan syndrome

目的对9例马凡综合征(Marfansyndrome,MFS)患者的原纤维蛋白-1(fibrillin-1,FBN1)基因进行突变筛查,以发现新的FBN1基因突变。方法应用变性高效液相色谱法对MFS患者FBN1基因65个外显子中的35个进行突变筛查,对变性高效液相色谱图形异常的PCR扩增片段用DNA测序鉴定突变位置及性质,并用等位基因特异性PCR以及限制性片段长度多态性分析等方法进一步证实突变。结果在两例MFS患者中发现两种新的FBN1基因突变。其中一种为第34外显子4307～4308位4个碱基TCGT的插入突变(4307insTCGT),另一种为第43外显子5309位的点突变5309G>A。结论FBN1基因移码突变(4307insTCGT)与点突变(5309G>A)分别是这两例MFS患者的发病原因。

Objective To detect novel mutations in the fibrillin 1( FBN1) gene by screening the gene from 9 patients with Marfan syndrome (MFS). Methods Denaturing high performance liquid chromatography (DHPLC) was used to screen for FBN1 mutation exon by exon. The DNA amplification fragments of which the DHPLC elution profiles showed difference in comparison with the corresponding normal elution profile were sequenced to identify the position and nature of mutation.The detected mutations were further proved by allele specific PCR or restriction fragment length polymorphism. Results Two novel FBN1 gene mutations were found and identified in two Marfan patients respectively,one of which was a small insertion in exon 34 at nucleotide 4307 4308 (4307insTCGT) and the other a missense mutation in exon 43 at nucleotide 5309 (5309G>A). Conclusion The findings suggested that the frameshift mutation (4307insTCGT) and point mutation (5309G>A) caused the corresponding patients to have MFS.