Investigation On Gene Mutations And Clinical Features Of Marfan Syndrome Among Han Population

ObjectiveThe purpose of this study was to detect mutations in fibrillin-1(FBN1), transforminggrowth factor beta receptor typeⅡ(TGFBR2) and transforming growth factor betareceptor typeⅠ(TGFBR1) genes from patients with Marfan syndrome (MFS) of Hanpopulation for investigating the nosogenesis and clinical features of the MFS patients.MethodsGenomic DNAs were extracted from whole blood sample of29MFS patients.All65exons of FBN1,9exons of TGFBR1and7exons of TGFBR2were amplified bypolymerase chain reaction (PCR) respectively, Followed by denaturing highperformance liquid chromatography (DHPLC)-DNA sequencing,to detect genemutations.Patients’samples with no FBN1mutation identified were further analyzedusing multiplex ligation-dependent probe amplification (MLPA) to detect deletemutation.Results1.A total of12FBN1mutations in12out of29patients were identified,in which8were de novel and4known.The mutations comprised7missense,2nonsense,2splicesite and1frameshift.The8newly found mutations were2359A>T (S787C),3380G>T(G1127V),4151T>C(M1384T),4244G>A(C1415Y),6071G>T(C2024F),IVS2+1G>T,IVS37+5G>A and7970C>G+7971delC.Besides,11polymorphisms in FBN1were found, of which6(IVS43-30delCCT,IVS45-63G>T, IVS47-28C>T, IVS52+127T>C,IVS52-23G>C,IVS57+63A>C) were first reporded.2. Out of4polymorphisms detected in TGFBR1,3were newly reported includingIVS6+109A>C,1032T>C(N344N) and1216T>C(L406L);In addition,4reported poly-morphism were found in TGFBR2.3.No delete mutation in FBN1and TGFBR2was detected by MLPA.4.Since2004,We have reported25FBN1mutations identified in MFS patients from Han population.Comparison analysis of clinical features showed that the frequencieswere lower for major skeletal criterion and ectopia lentis in this group than in theWestern MFS patients（12%vs32%;P <0.05and12%vs54%;P<0.01),While thefrequency was higher for dissection of ascending aorta than in Western MFS patients(48%vs14%;p<0.01).Conclusions1. DHPLC-DNA sequencing is a effecient and fast method for mutation detection andsuitable for gene diagnosis of MFS.2. FBN1mutation may be the pathogenesis of the12MFS patients.3. Some clinical features in Han patients with MFS differed from those reported inWestern MFS patients.