Clinical Analysis Of 15 Cases With Arrhythmogenic Right Ventricular Cardiomyopathy And Mutation Screening Of DSG2 In Patients

Arrhythmogenic right ventricular cardiomyopathy/dysplasia(ARVC/D) is characterized by progressive fibrofatty replacement of right ventricular myocardium, with autosomal dominant inheritance and incomplete penetrance.It may lead to RV dilatation and predispose to ventricular tachyarrhythmia originating from the RV. Patients with ARVC/D may present with palpitations,syncopal attacks,heart failure or even sudden cardiac death.ARVC/D was first described in 1982 when Marcus et al noticed a group of patients with RV dysplasia.These patients presented with ventricular tachycardia,supraventricular arrhythmias,right-heart failure or asymptomatic cardiomegaly.In these patients,the diagnosis was confirmed by eitherbiopsy or autopsy.Due to the broad spectrum of clinical manifestations,the Task Force of the European Society of Cardiology and International Society and Federation of Cardiology proposed diagnostic criteria in 1994,encompassing structural,functional and electrical aspects,and also integrating the histology and inheritance pattern.The pathogenesis of ARVC/D is not yet completely understood, but a genetic factor is knownto be involved.ARVC/D is inherited with an autosomal dominant pattern in some families.Linkage analysis studies have identified at least 11 loci for ARVC/D and some of the causal genes have been identified.Among these, the causal genes of ARVC/D 8-11 are desmoplakin(DSP),plakophilin-2(PKP2), desmoglein-2(DSG2) and desmocollin-2(DSC2) and they all encode major desmosomal component proteins.It is therefore postulated that disruption of the normal desmosome function plays an important role in the pathogenesis of ARVC/D. Inheritance of the ARVC/D is via an autosomal dominant mode of transmission.In recent years,dozens of mutations in desmosomal protein have been reported to link to ARVC/D,However,due to the lack of understanding of the correlation between gene mutation and the ARVC/D,genetic testing is only recommended for support of the clinical diagnosis,and early detection of relatives at potential risk.it will benefit screening of mutations of desmosomal protein and preparation for gene diagnosis and treatment.In the present study,we reported the clinical presentations,cardiac manifestations and desmosome gene mutations in ARVC/D patients in south of China. Most studies on ARVC/D have been performed in Western countries,and the clinical presentation and incidence of desmosome gene mutations remain unknown in our countries.This study was performed to determine possible ethnic or geographical differences.Objects1.To analysis the clinical characterics of ARVC/D in south of China.2.Screen DSG2 gene mutations in patients with ARVC/DMethods1,Clinical features were reevaluated in 15 patients diagnosed with ARVC/D in Department of Cadiology,Nanfang hospital from 2000 to 2007. 2.The results of analysis and statistical treatment:measurement data expresswith(?)±S and count data to the rate,Statistical analysis is dealt with statistical software SPSS13.0.3,Genomic DNA was extracted from peripheral blood of all of the patients who meant the diagnostic criteria of ARVC/D.25 pairs of PCR(polymerase chain reaction) primers were designed to amplify all 15 exons of DSG2 gene,then SSCP (single strand conformation polymorphism) electrophoresis were followed to determine the abnormal conformation of PCR products.If aberrant band was detected, DNA sequencing will be undertaken to confirm.Meanwhile,for those patients who had clear family history,PCR products were sequenced directly.DNA sequences were then analyzed for amino acids substitution.Any mutation will be compared with 200 unrelated healthy individuals to exclude genetic polymorphism.4.Results1.Clinical features were reevaluated in 15 patients diagnosed with ARVC/D in Department of Cadiology,Nanfang hospital f rom 2000 to 2007.To have statistic analysis and evaluate the effect of the treatment.Results In a coho rt of 15 patient s (7males),the mean age at t he time of hospitalization was(31.2±12.1) years, initial presentation mean age wa s(28.4±11.2)years.Three patients have family history.Six patients(40%) had a history of syncope.33.3%(5 cases) had only palpitations Only 1 patient was fo und epsilon waves in right precordial leads (V2～3),with T wave inversions.Abnormal echocardiography was found in 13 patients(86.6%),mainly RV dilation.4 patients received MRI with the features included:fat signal intensityof right ventricular(RV) wall(2 cases),thinningof RVwall(3 cases),declined ejection fraction of the RV(6 cases),For symptomatic patients,vent ricular arrhythmias were treated by amiodarone,β-blocker or other antiarrhythmia therapies.Antiarrhythmic drugs were ineffective in 46.6%(7/15) patients;3 cases of them were therefore treated by ablations.Nevertheless,VT recurred in 1 patient.Four patients were implanted cardial defibrillation (ICD).However,1 patient was implanted ICD twice because the battery was exhausted.2.There were no abnormal conformers were seen by PCR-SSCP analysis,A base mutation was identified by sequencing in one patient with family history.The mutation resultes in a G→C substitution in the first nucleotide of codon 861 of DSG2, but did't cause amino acid changing.5.Conclusion1,ARVC/D is characterised by ventricular arrhythmias.The diogrosis of ARVC/D depends on analysis of family history,history of syncope,ECG,echocardiography,cardiac MRI.The size of the right ventricle and out flow of right ventricle was significantly correlated with high-risk ARVC/D patients.Drug therapy is not up to our expectation.ablations or implant ICD can treat ventricular arrhythmias in order to reduce the incidence of sudden cardiac death.2,Mutation screening of DSG2 in patients had found SNP in DSG2,Howerve,in the 10 patients,no gene mutation was found in all of the exons of DSG2.3,The genetic characteristics of ARVC/D may have possible ethnic or geographical differences.