To investigate the mutation site of pathogenic gene in patients with hypertrophic cardiomyopathy (HCM) and to analyze the relationship between the genotype and clinical phenotype. Methods: Targeted exon capture sequencing was conducted in a HCM proband for 30 coding exons related HCM gene by all exon amplification and high-throughput sequencing. Furthermore, Sanger sequencing was performed in other family member and in 200 healthy volunteers for verification. The familial investigation included in clinical presentation, physical examination, electrocardiogram and echocardiography. Results: There were 3/6 blood relatives carrying cardiac myosin-binding protein gene MyBPC3 G772A heterozygous mutation, the mutation site was at 258 amino acid of MyBPC3 as glutamic acid (Glu) was substitute to lysine (Lys), such mutation was not found in rest of family member and not in healthy volunteers. The onset of proband and her daughter was rather late, they had palpitation and chest tightness; echocardiography showed interventricular septum basal segment thickening (16-18) mm. Proband was complicating paroxysmal ventricular tachycardia, malignant arrhythmia and heart failure, the maximum pressure gradient of left ventricular outflow was 56 mmHg, which with the high risk for sudden death. Conclusion: Comprehensive gene test has been helpful for clinical stratification, early diagnosis and treatment. MYBPC3 site mutation c.G772A might be the pathogenic mutation in that specific HCM family.

OBJECTIVE: To observe the conditions of sub-chronic crotonaldehyde exposure-induced pulmonary inflammation,oxidative stress and apoptosis in male rats,and to explore the related mechanisms. METHODS: The specific pathogen free Wistar male rats were randomly divided into control group,low-,medium-and high-dose crotonaldehyde groups,with 10 rats in each group. Rats were treated with crotonaldehyde at the concentrations of 0. 0,2. 5,4. 5 and 8. 5 mg/kg body weight by intra-gastric administration,once per day for 120 consecutive days. After the end of treatment,rats were sacrificed,the lungs were weighed and histopathological examination was performed. The levels of malondialdehyde( MDA),superoxide dismutase( SOD) and glutathione peroxidase( GSH-Px) in the serum of rats were determined by colorimetry. The relative expression of reactive oxygen species in lung tissues was detected by fluorescence probe. The apoptosis rate was detected by Tunel staining. The relative expression of B-cell lymphoma( Bcl)-2,Bcl-2 associated X protein( Bax) and cysteine aspartic acid protease-3( Caspase-3) proteins in lung tissue was detected by western blotting.RESULTS: The body weight of the rats in the high-dose group began to decrease after 30 days of exposure( P < 0. 05),and the body weight in the low-and medium-dose groups began to decrease at 90 days exposure( P < 0. 05),when compared with that of the control group at the same time. The body weight of the high-dose group was lower than that of the low-and medium-dose groups began to decrease at 90 days exposure( P < 0. 05). After exposure,the lung tissue of the three doses groups showed different degrees of inflammatory change in a dose-effect relationship. The level of serum MDA in rats increased with the treatment of crotonaldehyde( P < 0. 01). The activities of serum SOD and GSH-Px decreased with the treatment of crotonaldehyde( P < 0. 01). The relative expression of ROS and apoptosis rate in rat lung tissue increased with the treatment of crotonaldehyde( P < 0. 01). The relative expression of Bcl-2 protein and the ratio of Bcl-2/Bax in the lung tissue of rats decreased with the treatment of crotonaldehyde( P < 0. 01). The relative protein expression of Bax and Caspase-3 increased with the treatment of crotonaldehyde( P < 0. 01). CONCLUSION: Crotonaldehyde sub-chronic exposure can cause apoptosis in lung tissue by altering the oxidative balance,leading to inflammatory pathological changes in the lung.