Ligase chain reaction for diagnosis of familial hypertrophic cardiomyopathy

ＬｉｇａｓｅｃｈａｉｎｒｅａｃｔｉｏｎｆｏｒｄｉａｇｎｏｓｉｓｏｆｆａｍｉｌｉａｌｈｙｐｅｒｔｒｏｐｈｉｃｃａｒｄｉｏｍｙｏｐａｔｈｙＳｕｎＷｅｉｄｏｎｇ孙维东，ＨａｎｓｅｌＳｔｅｄｍａｎ，ＣｈｅｎＸｉａｏｌｉ，ＷｅｉＹｕ，ＬｉｕＭｅｉｚｈｅｎ，Ｘｕ...

Ligase chain reaction for diagnosis of familial hypertrophic cardiomyopathy

Objective To introduce the newly developed ligase chain reaction (LCR) method in the diagnosis of familial hypertrophic cardiomyopathy (FHC).Methods DNA and RNA from members of a family with patients having FHC were used to amplify β cardiac myosin heavy chain fragment by PCR. LCR was then used to detect the critical mutation in the FHC patient.Results By LCR, we screened the β cardiac myosin heavy chain genes of 19 members from one family with FHC. It is found that the mutation R249Q in the β cardiac myosin heavy chain gene was present in 10 members of the family. Clinical analysis of 10 adult patient relatives showed perfect agreement with clinical diagnosis (5 affected, and 5 not affected). In 9 other children (age, 1 to 20 years) within the family, only 2 had echocardiomyopathy. However, LCR analysis showed that 3 other children had also inherited the missense mutation and might later manifest the disease.Conclusions Our data suggest that LCR has great potential in the development of novel methods for diagnosing FHC. The detection of the disease-causing mutation could provide important prognostic information about affected members.