| Progress in the research on the molecular biology, medical genetics and imaging techniques of cardiovascular diseases has led to an improved understanding of Marfan syndrome and Liddle syndrome from clinical pathophysiology to molecular pathophysiology.Marfan syndrome (MFS) is an autosomal dominantly inherited connective tissue disorder characterized by cardiovascular, ocular and skeletal manifestations. Previously, mutations in the flbrlllln-1 (FBN1) gene on chromosome 15 have been reported to cause MFS. In the first part of the present study, a total of 21 unrelated patients with a possible or definite clinical diagnosis of MFS were investigated. Direct sequencing analysis was performed on the PCR sample. The analysis of genotype-phenotype correlations in MFS patients used data from this study and from the previous articles. The observed FBN1 mutations were consisted of 10 novel mutations(c.357 C>A,c.493 C>T, c.1374T>A, c.4143delG, c.6987 C>G, c.7238G>A, c.7765A>G, c.8200A>G, c.8431 G>A, c.8547 T>G,) and 2 reported mutations(c.4567C>T, c.4615C＞T). In the present study, we found that premature termination codon (PTC) mutations were associated with an increased risk of major cardiovascular involvement when compared with other mutations (78.3%vs. 68.1%; p=0.002). The percentage of patients with major cardiovascular involvement was higher in the group of patients with mutations in exons 24-32 when compared with mutations in exons 1-21(77.0% vs. 68.1%; p=0.04), and compared with exons 43-65(71.4% vs. 77.0%; p=0.133), but did not demonstrate this was significant.Liddle syndrome is an autosomal inheritable disease with severe hypertension, hypokalemia, suppressed plasma renin activity, low aldosterone secretion rates and early penetrance cardiovascular sequelae. It results from constitutive activation of the renal epithelial sodium channel(ENaC) due to mutation in either the beta subunit (SCNN1B; 600760) or the gamma subunit (SCNN1G; 600761) of this channel. In the second part of the present study, The mutation,P614L, is the first reported missense mutation in the PY motif of the human amiloride-sensitive epithelial sodium channel'sβsubunit causing Liddle syndrome. These findings provide further clinical evidence that this conserved PY motif is critical in the regulation of ENaC activity, permitting possible preclinical identification of subjects with a specific inherited susceptibility, and providing opportunities for the development of therapies specifically tailored to this underlying abnormality. Advances in the treatment of the syndrome have improved prognosis, but the long-term reoperation rate is still high. It remains unknown which factors influence the long-term prognosis, including the reoperation and mortality rates, in surgically treated Chinese patients with MFS. In the third part of the present study, we studied 125 such patients to investigate factors influencing prognosis after aortic surgery. The survival rate was 97.5%,91.4%, and 74.2% at 1,5,and 10 years after surgery, respectively. The reoperation rate was 2.5%,12.9%, and 32.9% at 1,5, and 10 years after surgery, respectively. Multivariate analysis revealed that increased systolic blood pressure (Sys BP) was the predictor of death (p<0.05), and body mass index and smoking were significant predictors of reoperation (p<0.05).In conclusion, these findings expand our understanding of the etiology, the molecular basis,the diagnosis and the treatment of MFS and Liddle syndrome. Molecular analysis of the disease causing gene enable a precise diagnosis of the syndrome and can be used for the diagnosis of the at-risk relatives,, and provide opportunities for the development of therapies specifically tailored to this underlying abnormality. The present findings also report the factors influencing the prognosis of Chinese patients with MFS after aortic surgical procedures. Managing these risk factors may enable health care professionals to improve the prognosis of MFS patients after aortic surgical procedures.
|
PDF Full Text Request