A novel phenotype with splicing mutation identified in a Chinese family with desminopathy / 中华医学杂志(英文版)

BACKGROUND@#Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations. Desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and arrhythmia. Combined with genotype, it helps us precisely diagnose and treat for desminopathy.@*METHODS@#Sanger sequencing was used to characterize DES variation, and then a minigene assay was used to verify the effect of splice-site mutation on pre-mRNA splicing. Phenotypes were analyzed based on clinical characteristics associated with desminopathy.@*RESULTS@#A splicing mutation (c.735+1G>T) in DES was detected in the proband. A minigene assay revealed skipping of the whole exon 3 and transcription of abnormal pre-mRNA lacking 32 codons. Another affected family member who carried the identical mutation, was identified with a novel phenotype of desminopathy, non-compaction of ventricular myocardium. There were 2 different phenotypes varied in cardiomyopathy and skeletal myopathy among the 2 patients, but no significant correlation between genotype and phenotype was identified.@*CONCLUSIONS@#We reported a novel phenotype with a splicing mutation in DES, enlarging the spectrum of phenotype in desminopathy. Molecular studies of desminopathy should promote our understanding of its pathogenesis and provide a precise molecular diagnosis of this disorder, facilitating clinical prevention and treatment at an early stage.

The relationship between the serum level of soluble ST2 and the severity and prognosis of heart failure / 天津医药

Objective To investigate serum levels of soluble matrix lysin 2 (sST2) in patients with different stages of heart failure and its relationship with prognosis. Methods Data of 300 patients with heart failure of stages A, B, C and D were included in this study. Thirty-three cases of healthy elderly population for physical examination were used as control group. The general information, echocardiography and related biochemical tests containing sST2 and NT-proBNP were collected in the two groups. The survival periods of patients were evaluated according to the Seattle heart failure mode (SHFM). Patients were followed up for 1 year to record the occurrence of adverse events. Results The sST2 level was higher in heart failure group than that of control group. The sST2 level began to increase in stage B, and which increased with the development of cardiac function staging. The sST2 levels were significantly higher in stages B, C and D than those of stage A, and which were significantly higher in stage D than those of stages B and C (P<0.05). There were significantly higher incidence rates of adverse events, left ventricular end diastolic diameter (LVEDD) and left ventricular mass index (LVMI) in the patients with high sST2 level than those of patients with lower sST2 level (P<0.05). Values of sST2, NT-proBNP, LVEDD and LVMI were significantly higher, and values of LVEF and SHFM life expectancy were significantly lower, in patients with adverse events than those of patients without adverse events (P<0.05). There was a negative correlation between sST2 and LVEF, and positive correlation between sST2 with NT-proBNP, LVEDD and LVMI (P<0.05). The size under ROC curve, which was used to predict the cardiovascular endpoint events judged by sST2 was 0.665 (95％CI:0.574-0.757, P<0.01), and the one by NT-proBNP was 0.790 (95％ CI: 0.731-0.848, P<0.01). The best cut-off value of predicting the clinical adverse events was 139.27μg/L by sST2 and 855.35μg/L by NT-proBNP. Conclusion The serum level of sST2 is early indicator of heart failure, which not only reflects the severity of ventricular remodeling but also is one of indicators to estimate the prognosis of heart failure in one year.