应用Ion Torrent半导体测序检测马凡综合征患者FBN1基因致病突变

Mutation detection of FBN1 in marfan syndrome patients by Ion Torrent semi-conductor sequencing

目的:对3个马凡综合征(MFS)家系及1例MFS患者的原纤维蛋白1基因(FBN1)进行基因检测,以明确致病突变,为患者提供遗传咨询及产前诊断。方法:应用高通量Ion Torrent半导体测序技术对3个MFS家系的先证者及1例MFS患者的FBN1基因进行检测,筛选致病突变位点,并用Sanger测序法验证。对1例胎儿FBN1基因相应的位点进行检测,以明确其受累情况。结果:患者P1 FBN1基因检测到c.7125_7126 del TG杂合性缺失突变,为可疑致病位点;家系1患者FBN1基因检测到IVS 27-1G>C(c.3464-1G>C)杂合性突变,为致病突变;家系2患者FBN1基因检测到c.4981G>C(p.Gly1661Arg)杂合性错义突变,为致病突变,胎儿携带同样突变;家系3患者FBN1基因检测到c.1546C>T(p.Arg516Term)杂合性无义突变,为致病突变。结论:应用高通量Ion Torrent半导体测序技术检测到3个MFS家系及1个MFS患者的致病基因突变,为临床诊断及遗传咨询提供分子遗传学依据,并对1例胎儿进行了产前诊断。

Objective：To identify pathogenic mutations of FBN1 in 3 Marfan syndrome （MFS） families and 1 MFS patient for genetic counseling and prenatal diagnosis. Methods：U- sing Ion Torrent semi-conductor sequencing to detect mutations of FBN1 in 3 Marfan syndrome （MFS） families and 1 MFS patient, then select pathogenic mutations, using Sanger sequencing to verify these mutations. Using Sanger sequencing to detect the corresponding site of FBN1 in the fetus. Results：we identified one probably pathogenic FBN1 mutation（ c. 7125_7126 del TG） in patient P1, one pathogenic FBN1 mutation（ IVS 27-1G〉C） in patients of family 1, one pathogenic FBN1 mutation（ c. 4981G〉C） in patient P6 and the fetus of family 2 ,one pathogen- ic FBN1 mutation（ c. 1546C〉T） in patients of family 3. Conclusion：We indentified pathogenic FBN1 mutations in 3 Marfan syndrome（MFS） families and 1 MFS patient, provided molecular genetic evidences for clinical diagnosis and genetic counseling, and made a prenatal diagnosis in one fetus.