Diagnosis And Pedigree Analysis Of Probands Of Marfan Syndrome Based On Genetic Testing

Objective:The probands of MFS were screened according to the diagnostic criteria of MFS,gene detection technology was used to draw gene mutation spectrum,and the undiscovered gene mutation sites were explored as well as the relationship between clinical phenotype and genotype.The members with atypical clinical symptoms in the proband’s family were screened for early diagnosis.Methods:Seven probands and family members who met the clinical diagnostic criteria of MFS were collected in our hospital.A total of thirty-five probands and family members were collected after signing the relevant informed consent form.Clinical signs and auxiliary examination data were collected,and DNA was extracted from peripheral venous blood of thirty-five people for gene sequencing and gene verification.According to the sequencing and validation results,relevant databases were searched to determine whether there were unreported mutation sites,and the correlation and difference between the mutation sites and clinical phenotypes in seven families were analyzed.At the same time,pedigree maps were drawn according to the verification results to screen out individuals with atypical clinical symptoms but consistent with genetic diagnosis.Results:Seven MFS probands were confirmed according to the diagnostic criteria of MFS,and Seven FBN1 mutations were detected by gene sequencing,including five heterozygous missense mutations: c.1645A>C(p.Thr549Pro)、c.3929G>T(p.Gly1310Val)、c.3914G>A(p.Cys1305Tyr)、 c.3043 G > A(p.Ala1015Thr)、 c.6947 G > T(p.Cys2316Phe).1heterozygous splicing site mutation: c.6496+5G>C;One large heterozygous fragment was missing: Ex43-Ex62Del;In addition,one CNV mutation was found on chromosome 15:46,Xn,del(15q21.1).Two different types of FBN1 mutations were screened out in the same individual: Ex43-Ex62 Del and c.3043G>A(p.Ala1015Thr).In three families,six members with FBN1 pathogenic mutation sites were screened but their clinical phenotypes did not meet the diagnostic criteria of MFS.Conclusion:1、Seven heterozygous mutation sites of FBN1 were screened out from seven MFS families by genetic detection technology,including one previously unreported missense mutation site of FBN1 and one previously unreported deletion site of large fragment of FBN1.A previously unreported CNV mutation site on chromosome fifteen enriches the mutation spectrum of MFS gene.2、Two different types of FBN1 mutations were screened out in the same individual,which provided a reference for the detection range of MFS pathogenic genes.3、There were individuals with atypical clinical symptoms but carrying pathogenic gene mutation sites in three MFS families.