Molecular Genetic Analysis Of Hypertrophic Cardiomyopathy And Wilson's Disease

There are two independent genetic project section in this thesis. The first project is to screen and detect the candidate genetic mutation for hypertrophic cardiomyopathy(HCM)in a Chinese family. The second project is to detect the major pathogenic mutaiton for Wilson's disease(WD) in a Chinese family.(1)HCM is a common type of heart disorder characterized with some degree of left ventricular hypertrophy.MYH7 gene encoding the ?-myosin heavy chain contractile protein is the most common gene for HCM whose mutations are pathogenic for 30~50%of all genotyped HCM cases. In this study, we identified a large family with HCM.Genetic studies revealed a novel Glu370Gln(E370Q) mutation located in exon 12 that was pathogenic for disease. The mutation ocurred at the evolutionarily conserved residue Glu370 in MYH7, and was not present in >500 normal control subjects. In conclusion,these results provide direct genetic evidence that the E370 Q may be pathogenic in this HCM family.(2)Wilson's disease(WD) is an autosomal recessive disorder of copper transport with hepatic and/or neurological symtoms. ATP7 B is the unique gene with several pathogenic variants known to cause WD. Some mutations are common while most reported mutations are rare, depending on the ethnical background and geographical location of the population. We identified a R778 L mutation in exon 8 of ATP7 B gene in a Chinese family of three generations. The R778 L is the most frequent mutation in Chinese patients with WD.These studies provide better understandings of the genetic basis of Chinese patients with HCM and WD, which have theory and application value for genetic testing,prognosis as well as therapeutic intervention.