Gene Mutation Study Of Familial Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is a myocardial disease characterized byenlarging the of left ventricular heart cavity and dysfunction of myocardial contraction.It is not clear about its etiology and pathogenesis. It may be csused by idiopathic factor,familial or genetic factor, immunological factor, virus infection, alcoholic or toxicfactor, perinatal period, etc. The incidence of DCM of China is19/100000. Themajority of patients have low five to ten years survival rate. Genetics researchindicates that genetic defects play an important role in the pathogenesis of FDCM.Objective: Collected general data of every member of a familial dilatedcardiomyopathy family, investigated the family and screened gene in order todetermine where the pathogenic gene mutation was.Methods: This study started with the proband based on a pedigee (the actualsampling number is45) with both DCM and atrioventricular block.The diagnosticcriteria for DCM according to WHO1995formulation is as follows:1. Leftventricular ejection fraction (LVEF)<45%；2. Left ventricular end diastolic diameter(LVEDd)>217cm/㎡or left ventricular end diastolic diameter (LVEDd)>55mm,3.Exclusion of hypertension, coronary atherosclerotic heart disease, alcoholiccardiomyopathy, pulmonary heart disease, congenital heart disease, myocarditis andother cardiovascular diseases and systemic diseases that may cause secondaryenlargement of the heart.According to the standard we collected data of regularphysical examination, electrocardiogram, echocardiography. It is necessar to work outthe Genealogical analysis and Pedigree chart based on the data we collected. First wecollected blood samples of the pedigee, extracted genomic DNA with phenol-chloroform. Then we sequenced the genome of LMNA. After this we sequencedDMD gene using multiplex ligation dependent probe amplification method. Linkageanalysis of X chromosome calculated the LOD score using Linkage Designer Version1software and Linkage Analysis Package5.1sofrware. Results: LMNA gene sequencing found no abnormal sequence, DMD gene hadno abnormal copy sequence. LOD of DXS1073on X chromosome was1.75.Conclusion: No mutations in LMNA gene, no deletion in DMD gene on the Xchromosome. LOD of DXS1073was higher. We speculated that the family genemutation was on the X chromosome, and should be in the vicinity of DXS1073. Theregion near the Xq28might be linked with mutation genes. Pathogenic gene mightnear the Xq28chromosome region.