Mutation analysis and prenatal diagnosis of FBN1 gene mutations for four patients with Marfan syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen for mutations of fibrillin-1 (FBN1) gene in 4 patients with Marfan syndrome in order to provide prenatal diagnosis and genetic counseling.</p><p><b>METHODS</b>Potential mutations of the FBN1 gene in the probands were detected with PCR and DNA sequencing. Subsequently, genomic DNA was extracted from amniotic fluid sampled between 18 to 20 weeks gestation. The mutations were confirmed with denaturing high-performance liquid chromatography - robust microsatellite instability (DHPLC-MSI) analysis with maternal DNA as reference. The products were further analyzed by direct sequencing and BLAST search of NCBI database.</p><p><b>RESULTS</b>An IVS46+1G>A substitution was identified in patient A at +1 position of intron 46 of the FBN1 gene. Two novel missense mutations were respectively discovered at positions +4453 of intron 35 in patient B (Cys1485Gly) and position +2585 of intron 21 in patient C (Cys862Tyr). In patient D, a novel deletion (c.3536 delA) was found at position +3536 of intron 28. In all of the 4 cases, the same mutations have been identified in the fetuses.</p><p><b>CONCLUSION</b>FBN1 gene analysis can provide accurate diagnosis of Marfan syndrome, which can facilitate both prenatal diagnosis and genetic counseling.</p>

Quantitative analysis of host cells growing into canine homograft valved aortic and pulmonary artery / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cryopreserved conduit valved homografts (CVH) have been widely used in surgical treatment of cardiac disease. This study aimed to determine the extent of host cell ingrowth and the durability and immunogenicity of CVH, and to compare the performance of CVH stored at 4°C and CVH cryopreserved in liquid nitrogen at -196°C.</p><p><b>METHODS</b>Heterotopic transplants of canine CVH stored at 4°C (n = 14) and cryopreserved in liquid nitrogen (n = 14) were made onto the abdominal aorta of recipient dogs. Animals were sacrificed at 7 and 15 days and at 1, 3, 6, 9, and 12 months after transplantation to excise the implanted CVHs. Tissue DNA extraction and quantitative polymerase chain reaction (PCR) were performed to calculate the ratio of donor cells and host cells in the CVH. The tissue viability of CVH after implantation was analyzed by detecting alkaline fibroblast growth factor 2 (FGF-2) using immunohistochemical staining and by observation under transmission electron microscope and scanning electron microscope.</p><p><b>RESULTS</b>All the animals survived and recovered well. There were few repopulating host cells (0.04% - 0.83%) in the implanted CVH at 7 or 15 days. The ratio of ingrowing host cells into the CVH continued rising after implantation and reached 40% - 47% in the 12th month postoperation. Histology, transmission electron microscopy and FGF-2 immunohistochemical staining indicated that fibroblasts and the host's endothelial cells were the main cellular elements invading the CVH. There were no significant differences in results between CVH stored at 4°C and CVH cryopreserved in liquid nitrogen.</p><p><b>CONCLUSIONS</b>Host cells growing into CVH are very important for maintaining the long-term structure and function of the implanted CVH. There is no significant difference between CVH storing at 4°C or in liquid nitrogen in regard to the ingrowth of host cells or of morphologic features after CVH allografting.</p>

Effect of pulmonary autograft transplantation in the surgical treatment of aortic valve disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Aortic root replacement with pulmonary autograft (Ross procedure) has the advantages of good haemodynamics and growth potential without the need for anticoagulation. In this study, we reviewed our experience of the Ross procedure for patients with aortic valve disease.</p><p><b>METHODS</b>From October 1994 to January 2005, 42 Ross procedures were performed in our centre. There were 30 males and 12 females. The mean age was 28 +/- 15 years (range, 5-56 years). Congenital heart disease (CHD) with aortic valve stenosis (AS) and/or aortic valve insufficiency (AI) in 40 cases including one associated with ventricular septal defect (VSD), degenerated aortic valve disease with AS in 1 and subacutive bacterial endocarditis (SBE) with AI in 1 were studied. The diagnosis was made by ultracardiography (UCG) in all patients. The mean aortic valve annulus diameter (AVD) was (2.45 +/- 0.31) cm and pulmonary valve annulus diameter (MPVD) was (2.34 +/- 0.21) cm. All patients had normal pulmonary valves. The New York Heart Association (NYHA) function class was II in 36 cases and III in 6 cases. The operation was performed under moderate hypothermic cardiopulmonary bypass (CPB) with aortic root replacement using pulmonary autograft and pulmonary valve replacement with a homograft.</p><p><b>RESULTS</b>There was no early hospital mortality. Postoperative UCG showed normal aortic valve function in all our patients. The mean gradient across the aortic valve was (6.11 +/- 0.12) mmHg. The left ventricular diastole diameter (LVDD) decreased significantly from (62 +/- 5) mm to (56 +/- 3) mm (P < 0.001). The mean postoperative left ventricular ejective fraction (LVEF) was 0.49 +/- 0.23. All patients were in NYHA class I-II. Follow-up was completed in 38 cases for a mean period of 3.2 years (range 1-10 years). All survivors were in NYHA class I with normal neo-aortic and pulmonary valve function. One patient died after secondary operation due to homograft fungal endocarditis 1 year after the Ross procedure. The cause of death was uncontrolled bleeding. Another patient suffered from cardiogenic shock and was on extracorporeal membrane oxygenation (ECMO) for 10 days postoperatively. This patient was subsequently self-discharged from hospital due to financial issues and he was excluded from follow-up.</p><p><b>CONCLUSION</b>The Ross procedure is an excellent technique to treat aortic valve disease. Our data show that it can be performed safely with good early and mid-term clinical outcomes.</p>