马方综合征临床实验室基因诊断

Clinical laboratory genetic diagnosis of Marfan syndrome

目的建立马方综合征(MFS)临床实验室基因诊断流程, 对MFS家系进行临床实验室基因诊断。方法利用二代高通量测序对2020年1月至12月到阜外华中心血管病医院(河南省人民医院心脏中心)就诊的2个MFS家系患者FBN1基因进行测序分析, 然后利用Sanger测序验证二代高通量测序结果, 同时对家系正常人及100名健康人进行突变位点Sanger测序以明确家系中FBN1基因致病性突变, 并于2个家系孕妇孕中期指导其进行产前诊断。结果 MFS临床实验室诊断显示2例MFS患者FBN1基因分别存在c.2560T>C 杂合突变、c.6772T>C杂合突变的致病性突变, 2个家系中正常人及100名健康人均未见此突变;产前诊断显示家系一胎儿存在FBN1基因c.2560T>C杂合突变, 为MFS患儿, 家系二胎儿FBN1基因未见突变, 建议继续妊娠, 产后随访结果与临床实验室诊断结果一致。结论成功建立了MFS临床实验室基因诊断流程, 对明确MFS临床诊断提供重要的参考依据。

Objective To establish the clinical laboratory genetic diagnosis procedures for Marfan syndrome(MFS)and carry out clinical laboratory genetic diagnosis for MFS families.Methods The second generation high-throughput sequencing was used to sequence and analyze the FBN1 gene of two MFS families who visited to Fuwai Central China Cardiovascular Hospital(Heart Center of Henan People′s Hospital)from January to December 2020,and then Sanger sequencing was used to verify the second generation high-throughput sequencing results.At the same time,the sanger sequencing of mutation sites was performed on normal family members and 100 healthy people to identify the pathogenic mutations of FBN1 gene in the MFS families.The pregnant women of two families were guided for prenatal diagnosis in the second trimester of pregnancy.Results The clinical laboratory diagnosis of MFS showed that two MFS patients had the pathogenic mutation of c.2560T>C heterozygous mutation and c.6772T>C heterozygous mutation in FBN1 gene,respectively.The mutation was not observed in 100 healthy people and normal members in two families.The prenatal diagnosis showed that there was a heterozygous mutation of FBN1 gene c.2560T>C in the first fetus of the MFS family,which was MFS.There was no mutation in the FBN1 gene in the second fetus of the MFS family,so it was recommended to continue the pregnancy.The results of postpartum follow-up were consistent with the results of clinical laboratory diagnosis.Conclusion The clinical laboratory genetic diagnosis procedures for MFS have been established successfully,which provides an important reference for clarifying the clinical diagnosis of MFS.