Different clinical characteristics and outcomes of hypertrophic cardiomyopathy with and without hypertension: seeking the truth.

OBJECTIVE: To determine the different clinical characteristics and outcomes of hypertrophic cardiomyopathy (HCM) patients with and without hypertension (HT). METHODS: A total of 696 HCM patients were included in this study and all HCM diagnoses were confirmed by the genetic test. Patients were analyzed separately in the septal reduction therapy (SRT) cohort and the non-SRT cohort. The primary endpoint was cardiovascular death and the secondary endpoint was all-cause death. Outcome analyses were conducted to evaluate the associations between HT and outcomes in HCM. Medications before enrollment and at discharge were collected in the post-hoc analyses. RESULTS: HCM patients without HT were younger, had a lower body mass index, were more likely to have a family history of HCM, and had a smaller left ventricular (LV) end-diastolic diameter than those with HT in both cohorts. A thicker LV wall, a higher level of N-terminal pro-B-type natriuretic peptide, and a higher extent of LV late gadolinium enhancement were additionally observed in patients without HT in the non-SRT cohort. The presence of HT did not alter the distribution pattern of late gadolinium enhancement, as well as the constituent ratio of eight disease-causing sarcomeric gene variants in both cohorts. Outcome analyses showed that in the non-SRT cohort, patients without HT had higher risks of cardiovascular death (HR = 2.537, P = 0.032) and all-cause death (HR = 3.309, P = 0.032). While such prognostic divergence was not observed in the SRT cohort. Further post-hoc analyses in the non-SRT cohort found that patients without HT received fewer non-dihydropyridine calcium channel blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers before enrollment and at discharge. CONCLUSIONS: HCM patients without HT had worse clinical conditions and higher mortality than patients with HT overall, which may result from active medical therapy in HT patients. Active SRT may have a substantial de-risking effect on patients meeting the indications.

Cardiac-specific Trim44 knockout in rat attenuates isoproterenol-induced cardiac remodeling via inhibition of AKT/mTOR pathway.

When pathological hypertrophy progresses to heart failure (HF), the prognosis is often very poor. Therefore, it is crucial to find new and effective intervention targets. Here, myocardium-specific Trim44 knockout rats were generated using CRISPR-Cas9 technology. Cardiac phenotypic observations revealed that Trim44 knockout affected cardiac morphology at baseline. Rats with Trim44 deficiency exhibited resistance to cardiac pathological changes in response to stimulation via isoproterenol (ISO) treatment, including improvement of cardiac remodeling and dysfunction by morphological and functional observations, reduced myocardial fibrosis and reduced expression of molecular markers of cardiac stress. Furthermore, signal transduction validation associated with growth and hypertrophy development in vivo and in vitro demonstrated that Trim44 deficiency inhibited the activation of signaling pathways involved in myocardial hypertrophy, especially response to pathological stress. In conclusion, the present study indicates that Trim44 knockout attenuates ISO-induced pathological cardiac remodeling through blocking the AKT/mTOR/GSK3ß/P70S6K signaling pathway. This is the first study to demonstrate the function and importance of Trim44 in the heart at baseline and under pathological stress. Trim44 could be a novel therapeutic target for prevention of cardiac hypertrophy and HF.

Using machine learning to aid treatment decision and risk assessment for severe three-vessel coronary artery disease.

BACKGROUND: Three-vessel disease (TVD) with a SYNergy between PCI with TAXus and cardiac surgery (SYNTAX) score of ≥ 23 is one of the most severe types of coronary artery disease. We aimed to take advantage of machine learning to help in decision-making and prognostic evaluation in such patients. METHODS: We analyzed 3786 patients who had TVD with a SYNTAX score of ≥ 23, had no history of previous revascularization, and underwent either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) after enrollment. The patients were randomly assigned to a training group and testing group. The C4.5 decision tree algorithm was applied in the training group, and all-cause death after a median follow-up of 6.6 years was regarded as the class label. RESULTS: The decision tree algorithm selected age and left ventricular end-diastolic diameter (LVEDD) as splitting features and divided the patients into three subgroups: subgroup 1 (age of ≤ 67 years and LVEDD of ≤ 53 mm), subgroup 2 (age of ≤ 67 years and LVEDD of > 53 mm), and subgroup 3 (age of > 67 years). PCI conferred a patient survival benefit over CABG in subgroup 2. There was no significant difference in the risk of all-cause death between PCI and CABG in subgroup 1 and subgroup 3 in both the training data and testing data. Among the total study population, the multivariable analysis revealed significant differences in the risk of all-cause death among patients in three subgroups. CONCLUSIONS: The combination of age and LVEDD identified by machine learning can contribute to decision-making and risk assessment of death in patients with severe TVD. The present results suggest that PCI is a better choice for young patients with severe TVD characterized by left ventricular dilation.

Myocardial tissue-specific Dnmt1 knockout in rats protects against pathological injury induced by Adriamycin.

Novel molecular mechanisms of the pathophysiology of heart failure (HF) are continuously being discovered, including epigenetic regulation. Among epigenetic marks, the role of DNA hypomethylation in shaping heart morphology and function in vivo and the pathogenesis of cardiomyopathy and/or HF, especially in adults, has not been clearly established. Here we show that the strong expression of DNA methyltransferase 1 (Dnmt1) is obviously downregulated in the WT adult rat heart with age. By contrast, the expression of Dnmt1 is upregulated suddenly in heart tissues from pressure overload-induced HF mice and adriamycin-induced cardiac injury and HF mice, consistent with the increased expression of Dnmt1 observed in familial hypertrophic cardiomyopathy (FHCM) patients. To further assess the role of Dnmt1, we generated myocardium-specific Dnmt1 knockout (Dnmt1 KO) rats using CRISPR-Cas9 technology. Echocardiographic and histopathological examinations demonstrated that Dnmt1 deficiency is associated with resistance to cardiac pathological changes and protection at the global and organization levels in response to pathological stress. Furthermore, Dnmt1 deficiency in the myocardium restricts the expressional reprogramming of genes and activates pathways involved in myocardial protection and anti-apoptosis in response to pathological stress. Transcriptome and genome-wide DNA methylation analyses revealed that these changes in regulation are linked to alterations in the methylation status of genes due to Dnmt1 knockout. The present study is the first to investigate in vivo the impact of genome-wide cardiac DNA methyltransferase deficiency on physiological development and the pathological processes of heart tissues in response to stress. The exploration of the role of epigenetics in the development, modification, and prevention of cardiomyopathy and HF is in a very preliminary stage but has an infinite future.

Han Chinese family with early-onset Parkinson's disease carries novel compound heterozygous mutations in the PARK2 gene.

PURPOSE: To identify deletions, duplications, and point mutations in 55 previously reported genes associated with Parkinson's disease (PD) and certain genes associated with tremor, spinocerebellar ataxia, and dystonia in a Han Chinese pedigree with early-onset Parkinson's disease (EOPD). PATIENTS AND METHODS: Clinical examinations and genomic analyses were performed on six subjects belonging to three generations of a Han Chinese family. Target region capture and high-throughput sequencing were used to screen these genes associated with PD, tremor, spinocerebellar ataxia, and dystonia. The multiplex ligation-dependent probe amplification (MLPA) method was applied to detect rearrangements in PARK2 exons. Direct Sanger sequencing of samples from all subjects further verified the detected abnormal PRKRA, SPTBN2, and ATXN2 gene fragments. RESULTS: Two family members were diagnosed with PD based on the clinical manifestations, imaging analyses. PARK2 gene heterozygous deletion of exon 3 and heterozygous duplication of exon 6 were identified in them (II-3 and 4). A single heterozygous deletion of exon 3 in PARK2 was detected in II-5 and III-10. A single duplication of exon 6 in PARK2 was detected in I1. Both the heterozygous mutation c.2834G>A (p. R945H) in exon 16 and the heterozygous mutation c.1924 C>T (p. R642W) in exon 14 of the SPTBN2 gene were identified in II-3, II-4, and III-10. The heterozygous mutation c.2989 C>T (p. R997X) in exon 24 of the ATXN2 gene was detected in II-4 and II-5, and the heterozygous mutation c.170 C>A (p. S57Y) in exon 2 of the PRKRA gene was detected in II-3, II-4, and III-10. Other mutations in some genes associated with PD, tremor, spinocerebellar ataxia, and dystonia were not detected. CONCLUSIONS: Novel compound heterozygous mutations were identified in a Han Chinese pedigree and might represent a cause of EOPD.

Familial hypertrophic cardiomyopathy caused by a de novo Gly716Arg mutation of the ß-myosin heavy chain.

The present study was performed to identify the genotype of a hypertrophic cardiomyopathy family and investigate the clinicopathogenic characteristics and prognostic features of relevant genetic abnormalities. Target sequence capture sequencing was performed to screen for pathogenic alleles in a 32-year-old female patient (proband). Sanger sequencing was carried out to verify the results. Sanger sequencing was also performed on other family members to identify allele carriers. A survival analysis was carried out using published literature and our findings. We found that the proband and her son harboured a Gly716Arg sequence variant of the ß-myosin heavy chain. Neither the proband's father nor the mother were carriers of this sequence variant; thus, the mutation was classified as "de novo". Further survival analysis revealed that female patients appear to have a longer life expectancy compared with males. Our study may provide an effective approach for the genetic diagnosis of hypertrophic cardiomyopathy.

Myocardial bridging as a common phenotype of hypertrophic cardiomyopathy has no effect on prognosis.

BACKGROUND: The prognostic significance of myocardial bridging in hypertrophic cardiomyopathy (HCM) remains controversial. This investigation sought to evaluate the impact of myocardial bridging on prognosis of patients with HCM. METHODS: A total of 298 adult patients (73% male, mean age, 53 ± 12 years) with HCM were retrospectively enrolled at Fuwai Hospital from 1999 to 2011. Myocardial bridging was evaluated by coronary angiography. Follow-up data were collected by telephone interviews and mailed questionnaires. RESULTS: Thirty-four (11%, 34/298) patients were determined with myocardial bridging and the middle of left anterior descending artery was the most frequently involved segment (77%, 26/34). Patients with myocardial bridging were younger than those without bridging (48 ± 9 versus 54 ± 12 years, P = 0.001). During the follow-up of 4.2 ± 2.3 years (range, 0.7-12.2 years), the presence of myocardial bridging was not evidently associated with increased risk for all-cause death (P = 0.54), cardiovascular death (P = 0.60), sudden cardiac death (P = 0.53) and deterioration of heart failure (P = 0.84). CONCLUSIONS: Myocardial bridging was a relatively common morphological component of HCM but not a predictor for adverse clinical outcomes.

Screening of pathogenic genes in Chinese patients with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiac disease predominantly caused by mutations in desmosomal protein genes. Previous genetic analyses of the Chinese ARVC population are limited to small size and restriction to a single gene. This study was aimed to investigate the genotype in a large series of Chinese patients with ARVC through comprehensively screening nine ARVC-causing genes. METHODS: A total of 100 unrelated ARVC patients and 300 age, gender and ethnicity matched healthy controls were genetically tested with multiplexing targeted resequencing for nine previously reported ARVC-causing genes, including plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2, plakoglobin, transforming growth factor beta-3, transmembrane protein 43, desmin and Lamin A/C. RESULTS: Fifty-nine mutations were identified in 64% of the patients, among which, 93% were located in desmosomal protein genes. Plakophilin-2 mutations accounted for 54% of the total and 58% of the desmosomal mutations, with a truncating mutation type making up about 2/3 of the plakophilin-2 mutations. Only four mutations were found in non-desmosomal genes; two in transmembrane protein 43 and two in transforming growth factor beta-3. Two of them (one of each gene) appeared as single missense mutations. No mutation was identified in desmin or Lamin A/C. Multiple mutations were found in 23% of the patients, with plakophilin-2 being found in 57% of the multi-mutation carriers. CONCLUSIONS: Plakophilin-2 was the most common gene mutation that was identified in Chinese ARVC patients. Non-desmosomal genes should be added to desmosomal protein genes when performing molecular genetic screening in patients with suspected ARVC.

Methylation of FOXP3 in regulatory T cells is related to the severity of coronary artery disease.

OBJECTIVES: Regulatory T (Treg) cells have been shown to play a protective role in experimental atherosclerosis. However, it is unclear whether Tregs can protect from rupture of vulnerable plaque in patients with atherosclerosis. Demethylation of the DNA encoding the transcription factor forkhead box P3 (FOXP3) was found to be essential for the stable maintenance of the suppressive properties of Tregs. We aimed to evaluate Treg levels in patients with acute coronary syndrome (ACS) using a method based on Treg-specific DNA demethylation within the FOXP3 gene. METHODS AND RESULTS: Peripheral blood was collected to determine Treg levels by PCR-based DNA methylation analysis. We found that Treg levels were decreased in patients with ACS compared with normal coronary controls. The decrease in Tregs was associated with the severity of the ACS. Furthermore, up-regulation of DNA-methyltransferases was detected in CD4(+)CD25(+) Tregs obtained from ACS patients as compared to those from normal coronary controls. A dose-dependent increase in the methylation of the Treg-specific demethylated region in FOXP3 was observed in cultures of PBMCs with ox-LDL. Moreover, the ox-LDL-induced Treg effects could be restored by loading (-)-epigallocatechin-3-gallate, a methyltransferase inhibitor. Treatment of CD4(+)CD25(+) Tregs with ox-LDL resulted in a 41% increase in the methylation of FOXP3, a 66% of reduction in FOXP3 mRNA expression, and an increase in the expression of DNA methyltransferase 3a as well as 3b. CONCLUSIONS: Our data demonstrate that reduction in Treg cells is associated with ACS in atherosclerotic patients. Epigenetic suppression of FOXP3 might lead to down-regulation of Treg cells, and in turn increase the risk of ACS.

[Comparison of clinical characteristics of Chinese patients with apical hypertrophic cardiomyopathy and typical hypertrophic cardiomyopathy].

OBJECTIVE: To evaluate the clinical features in Chinese patients with apical hypertrophic cardiomyopathy (AHCM) and typical hypertrophic cardiomyopathy (HCM). METHODS: This retrospective analysis included 160 patients hospitalized in Fuwai hospital. Patients were divided into three groups: apical hypertrophic cardiomyopathy (AHCM, n = 41) group, non-obstructive typical hypertrophic cardiomyopathy group [NOHCM, LVOT < 30 mm Hg (1 mm Hg = 0.133 kPa) at rest, n = 52] and obstructive typical hypertrophic cardiomyopathy (OHCM, LVOT ≥ 30 mm Hg at rest, n = 67). Clinical features, diagnosis, therapy, and plasma levels of biomarkers of these three groups were analyzed. RESULTS: (1) The age at disease onset was older in AHCM group than in OHCM group [(49.9 ± 13.6) years vs. (41.4 ± 14.6) years, P < 0.01]. Exertional dyspnea appeared more often in HCM patients than in AHCM patients, NT-proBNP level was significantly lower in AHCM patients than in OHCM patients (P = 0.001). Plasma CK-MB, LDH, TnI and MYO levels were similar among the three groups. (2) Thirty-three AHCM patients were first hospitalized for suspected coronary heart disease (CHD) and CHD was excluded in 18 cases (43.9%). (3) The frequency of giant negative T waves (depth ≥ 10 mm) on ECG was 43.9%, 13.5% and 4.4% (P < 0.01) in AHCM, NOHCM and OHCM respectively. Half of AHCM patients showed left ventricular high voltage on ECG. (4) Cardiac magnetic resonance imaging is superior to echocardiography on correctly diagnosing AHCM. CONCLUSION: AHCM patients differ from typical OHCM patients in clinical characteristics. There were significant differences on echocardiography and electrocardiography features among three groups. Cardiac magnetic resonance imaging and giant negative T waves on ECG are helpful for the diagnosis of AHCM.

[The genotype-phenotype correlation of the MYH7 gene c.1273G > a mutation in familial hypertrophic cardiomyopathy].

To investigate the genotype-phenotype correlation in Chinese familial hypertrophic cardiomyopathy (HCM), peripheral blood samples were collected from 7 members of a Chinese HCM family, and 120 normal subjects were recruited as control. The full encoding exons and flanking sequences of the cardiac troponin T (TNNT2) gene, beta-myosin heavy chain (MYH7) gene and myosin binding protein C (MYBPC3) gene were amplified and the products were sequenced directly to detect the mutations. A missense mutation, c.1273G>A, was identified in exon 14 of the MYH7 gene in 4 members of the Chinese HCM family, which resulted a glycine (Gly) to arginine (Arg) exchange at amino acid residue 425. The 425th glycine amino acid residue is highly conservative across the different species. The clinical phenotypes among the family members who carried this mutation presented significant individual differences. The c.1273G>A mutation of the MYH7 gene might be the causal mutation of the familial HCM. The heterogeneity of phenotypes suggested that multiple factors may be involved in the pathogenesis of HCM.

[A novel hot-spot mutation S236G in the cardiac myosin binding protein C gene in Chinese patient with hypertrophic cardiomyopathy].

OBJECTIVE: To identify the disease-causing gene mutations and to reveal the relationship between the genotype and the phenotype in Chinese patients with hypertrophic cardiomyopathy (HCM). METHODS: One hundred unrelated patients with HCM and 120 controls were enrolled in this study. The full encoding exons and flanking sequences of the cardiac myosin binding protein C gene (MYBPC3) were amplified with PCR and the products were sequenced. RESULTS: A novel missense mutation c.706T > C was identified in exon 6 of MYBPC3 gene in three HCM patients, which resulted a Serine (S) to Glycine (G) exchange at amino acid residue 236 (S236G). The clinical phenotypes of the three patients were different (2 obstructive HCM, 1 non-obstructive HCM). The 120 controls were normal in the genetic test. CONCLUSIONS: The novel S236G mutation in MYBPC3 gene was a hot-spot mutation in Chinese patients with HCM.

[The genotype-phenotype correlation of MYH7 gene G15391A mutation and MYBPC3 gene G12101A mutation in familial hypertrophic cardiomyopathy].

OBJECTIVE: To reveal genotype-phenotype correlation of disease-causing gene mutations in Chinese hypertrophic cardiomyopathy (HCM) pedigree. METHODS: Peripheral venous blood samples were collected from two Chinese HCM families and 120 healthy subjects were recruited as normal control. The full encoding exons and flanking sequences of the cardiac troponin T gene (TNNT2), beta-myosin heavy chain gene (MYH7) and myosin binding protein C gene (MYBPC3) were amplified with the polymerase chain reaction method, DNA sequencing was used to detect the mutation. RESULTS: In ZZJ family, mutation G12101A was identified in exon 21 of MYBPC3 gene in 4 family members [the arginine (R) converted to histidine (H)]. In this pedigree, three out of eight family members were diagnosed as HCM and with a penetrance of 75%. In FHL family, mutation G15391A was identified in exon 23 of MYH7 gene in 3 family members [the glutamic acid (E) converted to lysine (K)]. In this pedigree, three out of six family members were diagnosed as HCM and with a penetrance of 100%. Echocardiography showed obstruction of left ventricular outflow tract in two out of the three HCM patients. CONCLUSIONS: Our results showed that the G12101A mutation of MYBPC3 gene is the causal mutation of familial HCM with mild phenotype. The G15391A mutation of MYH7 gene is the causal mutation of familial HCM with malignant phenotype and a penetrance of 100%. Screening mutations in the MYH7 gene should be viewed as a reasonable procedure in obstructive HCM patients.

[Genetic heterogeneity of myosin heavy chain 7 gene G823E mutation in familial hypertrophic cardiomyopathy in Chinese].

OBJECTIVE: To study the disease-causing gene mutations in familial hypertrophic cardiomyopathy (HCM) in Chinese and to reveal the relationship between the genotype and the phenotype. METHODS: Peripheral blood samples were collected from 12 members of a HCM family, and 120 healthy volunteers in China. PCR and double deoxygenation chain termination method were used to analyze the cardiac troponin T gene (TNNT2), beta-myosin heavy chain gene (MYH7) gene and myosin binding protein C gene (MYBPC3) and to detect mutations. RESULTS: Mutation G14452A was identified in exon 22 of MYH7 gene in 4 family members, causing the conversion of glycine (G) into glutamic acid (E). The onset ages and clinical manifestations of the family members carrying the mutation G823E, including 2 patients (the proband, male, with the onset age of 51, and his 26-year-old second son with the onset age of 20), and 2 carriers (his 31-year-old elder son and 29-year-old elder daughter), presented significant individual differences. CONCLUSIONS: The G823E mutation of MYH7 gene is the causal mutation of familial HCM. The heterogeneity of phenotypes suggests that multiple factors may be involved in the pathogenesis of HCM.

[Family hypertrophic cardiomyopathy caused by a 14035c > t mutation in cardiac troponin T gene].

OBJECTIVE: To study the disease-causing gene mutation in Chinese patients with familial hypertrophic cardiomyopathy (FHC) and to analyze the correlation between the genotype and the phenotype. METHODS: Peripheral blood samples were collected from 40 members from a family affected with FHC, and 120 healthy volunteers. PCR was performed to analyze the exons and flanking introns of the cardiac troponin T gene (TNNT2), beta-myosin heavy chain gene (MYH7), and myosin-binding protein C gene (MYBPC3) and the products were sequenced. The clinical data including symptom, physical examination, echocardiography and electrocardiography were collected. RESULTS: A 14035c > t mutation, which causes a missense mutation (R130C) in exon 10 of TNNT2 gene were identified in 4 family members, including the proband, female, aged 53, with the onset at the age of 30. The 4 persons with the 14035c > t mutation, all FHC patients, presented left ventricular dysfunction with a penetrance of 100%. Two of the patients died of sudden cardiac death during follow-up. No mutation was identified in the MYH7 and MYBPC3 genes. CONCLUSION: The 14035c > t mutation of TNNT2 gene is the causal mutation of FHC which is associated with malignant phenotype with a penetrance of 100%. It is a reasonable procedure in HCM patients with malignant phenotype to screen mutation in the TNNT2 gene.

[Clinical features of dilated cardiomyopathy-like hypertrophic cardiomyopathy caused by a 13261 G > A mutation in cardiac myosin-binding protein C gene].

OBJECTIVE: To study the disease-causing gene mutation in Chinese patients with hypertrophic cardiomyopathy (HCM) and to analyze the genotype and phenotype correlation. METHODS: One family (n = 27) affected with HCM were chosen for the study. The full encoding exons and flanking sequences of beta-myosin heavy chain gene (MYH7) and cardiac myosin-binding protein C gene (MYBPC3) were amplified with PCR and the products were sequenced. The clinical data including symptom, physical, echocardiography and electrocardiography examinations were collected. RESULTS: We identified a 13261 G > A mutation, which causes a missense mutation (G758D) in exon 23 of MYBPC3 in 9 family members. One mutation carrier suffered from dilated cardiomyopathy (DCM) with asymmetric interventricular septal hypertrophy (14 mm). Another mutation carrier was diagnosed as HCM. CONCLUSIONS: The 13261 G > A mutation is associated with a DCM-like HCM and HCM phenotype in this Chinese family affected with HCM.

[Familiar hypertrophic cardiomyopathy caused by a IVS15-1G > A mutation in cardiac myosin-binding protein C gene].

OBJECTIVE: To detect the disease-causing gene mutation of hypertrophic cardiomyopathy (HCM) in a Chinese family and to analyze the correlation of the genotype and the phenotype. METHODS: One family affected with HCM was studied. The clinical data including symptom, physical examination, echocardiography and electrocardiography were collected. The full encoding exons and flanking sequences of beta-myosin heavy chain gene (MYH7) and cardiac myosin-binding protein C gene (MYBPC3) were amplified with PCR and the products were sequenced. RESULTS: A G8887A mutation, which is an acceptor splicing site of intron 15 (IVS15-1G > A) in MYBPC3 (gi: Y10129) was identified in 6 out of 11 family members. Three mutation carriers developed HCM at 48 - 75 years old with mild chest pain, chest distress and asymmetric septal hypertrophy (13 - 14 mm) and remaining mutation carriers are free of HCM. No mutation was identified in MYH7 gene. CONCLUSION: HCM caused by the IVS15-1G > A mutation is a benign phenotype. It is helpful to screen MYBPC3 gene mutation in late-onset HCM patients with mild symptoms.

[A novel LMNA gene mutation E82K associated with familial dilated cardiomyopathy].

OBJECTIVE: To examine the function of the novel mutation E82K in LMNA gene identified in a Chinese family infected by dilated cardiomyopathy. METHODS: (1) One Chinese family infected by dilated cardiomyopathy was chosen for the study. Exons 1-12 of the LMNA gene were screened with both PCR method and the cycle sequencing of the PCR products. (2) cDNA of the E82K mutation or wild type of LMNA gene was transfected into HEK293 cells and the apoptosis of the cells was detected after treatment with 0.8 mmol/L H2O2. RESULTS: (1) A new mutation E82K in LMNA gene was identified in this dilated cardiomyopathy family. (2) Apoptosis was more in the HEK293 cells transfected with E82K mutation than those with empty vector or wild type LMNA gene. CONCLUSIONS: The missense mutation E82K in LMNA gene changed the polar of the amino acid. It showed a malignant phenotype of severe clinical symptoms, early onset, poor survival prognosis and might be associated with atrioventricular conduction block (II degrees-III degrees), suggesting that the E82K mutation in LMNA gene may be a candidate for nosogenesis of dilated cardiomyopathy.