Abstract 1055: Prevalence of Lamin A/C Gene Mutations in Familial Dilated Cardiomyopathy with Progressive Atrioventricular Block in Japan
Background: Lamin A/C gene (LMNA) mutations can cause dilated cardiomyopathy (DCM) with atrioventricular block (AVB). Patients with LMNA mutations die suddenly even after pacemaker implantation. Previously it has been reported that LMNA mutations account for 33% of DCM with AVB in Italy, and survival rate of LMNA mutation carriers at the age of 50 was about 62% in North America and Europe. We suppose that screening of LMNA mutations is useful for risk stratification of DCM patients with AVB. However, it remains to be examined whether the LMNA is a major gene responsible for familial DCM with progressive AVB in Japan as well.
Methods: We included 357 DCM patients from 26 hospitals in Japan from 2000 to 2003, and identified familial DCM with progressive AVB using medical and family history taking, electrocardiography and echocardiography. The inclusion criteria were as follows;
left ventricular ejection fraction < 50% and/or left ventricular end-diastolic diameter > 55mm, and
family history of AVB and/or bradycardia due to atrial fibrillation among the first degree relatives.
Written informed consent was obtained from all participants under approval of the ethics committee of the Tohoku University School of Medicine. Genomic DNA was extracted from peripheral white blood cells. Twelve exons of LMNA were amplified by polymerase chain reaction and directly screened by cycle sequencing.
Results: In the 357 DCM patients, we identified 5 probands of the familial DCM with progressive AVB (5/357; 1.4%). In 3 of the 5 families, we identified different mutations, including 2 novel mutations, IVS3–10A > G, 815– 818delinsCCAGAC, and R166P, respectively. The LMNA mutations accounted for 0.8% (3/357) of DCM and 60% (3/5) of familial DCM with progressive AVB. Survival rate of patients with LMNA mutations at the age of 50 was 53%.
Conclusions: These results indicate that LMNA mutations are detected in the familial DCM with AVB and that the patients with LMNA mutations have a poor prognosis in Japan at the similar level as in North America and Europe. Screening for LMNA mutation may be important for risk stratification of DCM patients, especially for those with AVB.