Association Between DSCR1 Variations and Congenital Heart Disease Susceptibility.

BACKGROUND The objective of this study was aimed to detect the association of Down syndrome critical region 1 (DSCR1) gene polymorphisms (rs149048873 and rs143081213) and congenital heart disease (CHD) susceptibility. MATERIAL AND METHODS This case-control study included 102 CHD patients and 113 healthy controls. Cases and controls were matched in age and gender. Genotypes of DSCR1 gene polymorphisms were detected by TaqMan method in cases and controls. Hardy-Weinberg equilibrium (HWE) examination was performed by PLINK 1.0 software. Chi square test was utilized to assess the distribution of the genotypes and the alleles. Relative risk of CHD was presented by odds ratios (ORs) with 95% confidence intervals (CIs). All of the calculations were implemented using SPSS 18.0. RESULTS Variant genotype distribution of rs149048873 and rs143081213 mutations were higher in cases than in controls, but the differences were not statistically obvious (P>0.05). Additionally, frequencies of mutant allele of the two polymorphisms were also significantly different in case and control groups (P>0.05). CONCLUSIONS No significant associations existed between DSCR1 gene rs149048873 and rs143081213 polymorphisms and CHD susceptibility.

Design and preparation of polyurethane-collagen/heparin-conjugated polycaprolactone double-layer bionic small-diameter vascular graft and its preliminary animal tests.

BACKGROUND: People recently realized that it is important for artificial vascular biodegradable graft to bionically mimic the functions of the native vessel. In order to overcome the high risk of thrombosis and keep the patency in the clinical small-diameter vascular graft (SDVG) transplantation, a double-layer bionic scaffold, which can offer anticoagulation and mechanical strength simultaneously, was designed and fabricated via electrospinning technique. METHODS: Heparin-conjugated polycaprolactone (hPCL) and polyurethane (PU)-collagen type I composite was used as the inner and outer layers, respectively. The porosity and the burst pressure of SDVG were evaluated. Its biocompatibility was demonstrated by the 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H tetrazolium bromide (MTT) test in vitro and subcutaneous implants in vivo respectively. The grafts of diameter 2.5 mm and length 4.0 cm were implanted to replace the femoral artery in Beagle dog model. Then, angiography was performed in the Beagle dogs to investigate the patency and aneurysm of grafts at 2, 4, and 8 weeks post-transplantation. After angiography, the patent grafts were explanted for histological analysis. RESULTS: The double-layer bionic SDVG meet the clinical mechanical demand. Its good biocompatibility was proven by cytotoxicity experiment (the cell's relative growth rates (RGR) of PU-collagen outer layer were 102.8%, 109.2% and 103.5%, while the RGR of hPCL inner layer were 99.0%, 100.0% and 98.0%, on days 1, 3, and 5, respectively) and the subdermal implants experiment in the Beagle dog. Arteriography showed that all the implanted SDVGs were patent without any aneurismal dilatation or obvious anastomotic stenosis at the 2nd, 4th, and 8th week after the operation, except one SDVG that failed at the 2nd week. Histological analysis and SEM showed that the inner layer was covered by new endothelial-like cells. CONCLUSION: The double-layer bionic SDVG is a promising candidate as a replacement of native small-diameter vascular graft.

Association of NFATc1 gene polymorphism with ventricular septal defect in the Chinese Han population.

BACKGROUND: Congenital heart disease (CHD) is a diverse group of diseases determined by genetic and environmental factors. Considerable research has been done on genes associated with the development of the heart. Recently, focus is on the role of transcription factor NFATc1 in the development of proper valve and septa. As part of a larger study, high density single nucleotide polymorphism (SNP) scanning was used to explore the relationship between NFATc1 gene polymorphism and susceptibility to ventricular septal defect (VSD) in the Chinese Han population. METHODS: One hundred and ninety-two pediatric patients with congenital VSD and 192 matching healthy control subjects were studied. The haplotype reconstructions were calculated by PHASE2.0 software. Haploview software was used to perform linkage disequilibrium assessment and define haplotype blocks. The algorithm used for defining the blocks was the confidence interval method. RESULTS: The NFATc1 gene region can be divided into 11 haplotype blocks. Strong linkage disequilibrium existed within blocks 6, 8, 9, and 11. Three SNPs (rs7240256, rs11665469, and rs754505) within the NFATc1 gene had significant correlation with VSD by single marker association analysis. In addition, two haplotypes correlated with VSD. CONCLUSIONS: NFATc1 is associated with the occurrence of VSD and it may be a predisposing gene to CHD in Han Chinese. This finding has set a direction for further genetic and functional studies.

Surgical treatment for vascular anomalies and tracheoesophageal compression.

BACKGROUND: Vascular rings are uncommon anomalies in which preferred strategies for diagnosis and management may vary among institutions. In this study, we reported our approach and a review of our 5-year experience. METHODS: From May 2006 to April 2011, 45 children (31 boys) with vascular rings underwent surgical repair at Beijing Children's Hospital. Nineteen patients (26%) had associated heart anomalies. RESULTS: There were two hospital deaths. At follow-up, 11 patients still had intermittent respiratory symptoms, but these symptoms had no effect on growth or physical activities. No patients required reoperation. CONCLUSIONS: The rates of misdiagnosis and missed diagnosis of vascular rings are higher than those of other congenital heart diseases. A high index of clinical suspicion coupled with the use of computed tomography enables early diagnosis. Surgical repair can be performed successfully, although a number of patients will have persistent symptoms.

Transcription factor HAND2 mutations in sporadic Chinese patients with congenital heart disease.

BACKGROUND: The basic helix-loop-helix transcription factor HAND2 plays an essential role in cardiac morphogenesis. However, the prevalence of HAND2 mutations in congenial heart disease (CHD) and the correlation between the HAND2 genotype and CHD phenotype have not been studied extensively. METHODS: We amplified the exons and the flanking intron sequences of the HAND2 gene in 131 patients diagnosed with congenital defects of the right ventricle, outflow tract, aortic artery or cardiac cushion and confirmed the mutations by sequencing. RESULTS: Seven mutations including three missense mutations (P11R, S36N and V83L), one isonymous mutation (H14H) and three mutations in untranslated region (241A > G, 604C > T and 3237T > A) were identified in 12 out of the 131 patients. Both nonisonymous mutations are located in the transcriptional activation domain on the N-terminus. Only one mutation (S36N) was identified in 250 normal healthy controls. The distribution of 3637T > A is the unique one which was different between the 2 groups. CONCLUSIONS: HAND2 may be a potential candidate gene of stenosis of the right ventricle, outflow tract. Further study of those with a family history of HAND2 mutations will help convincingly relate their genotype to the pathogenesis of CHD.

GATA4 and NKX2.5 gene analysis in Chinese Uygur patients with congenital heart disease.

BACKGROUND: Congenital heart disease (CHD) is the most common developmental anomaly in newborns. The germline mutations in GATA4 and NKX2.5 genes have been identified as responsible for CHD. The frequency of GATA4 and NKX2.5 mutations in Chinese Uygur patients with CHD and the correlation between their genotype and CHD phenotype are unknown. METHODS: We examined the coding region of GATA4 and NKX2.5 genes in 62 Chinese Uygur patients with CHD and 117 Chinese Uygur individuals as the controls by denaturing high performance liquid chromatography (DHPLC) and sequencing. RESULTS: Two heterozygous missense mutations of c.1220C > A and c.1273G > A in GATA4 gene, which cause the amino acid residue changes of P407Q and D425N in GATA4, were found in a patient with tetralogy of Fallot and a patient with ventricular septal defect, respectively. The two patients did not have atrioventricular conduct defects or non-cardiac abnormalities. The two mutations are expected to affect the protein function. There were no reported NKX2.5 mutations in the patients. CONCLUSION: Our results provided the primary data on CHD phenotype associated with GATA4 mutation in the Chinese Uygur population.

Association of TBX5 gene polymorphism with ventricular septal defect in the Chinese Han population.

BACKGROUND: Congenital heart disease is a diverse group of diseases determined by genetic and environmental factors. Considerable research has been done on genes associated with development of the heart. A recent focus is the role of transcription factor TBX5 in the development of atria, left ventricle and conduction system. As part of a larger study, high density, single nucleotide polymorphism (SNP) scanning was used to explore the relationship between TBX5 gene polymorphism and susceptibility to ventricular septal defect not associated with forelimb malformation in the Chinese Han population. METHODS: One hundred and ninety two paediatric patients with congenital ventricular septal defect and 192 matched healthy control subjects were studied. The haplotype reconstructions were calculated by PHASE2.0 software. Haploview software was used to perform linkage disequilibrium assessment and defining of haplotype blocks. The algorithm used for defining of blocks was the confidence interval method. RESULTS: The TBX5 gene region can be divided into 3 haplotype blocks of 27, 15 and 2 SNPs. Strong linkage disequilibrium exists within each block. SNP rs11067075 within the TBX5 gene had significant correlation with ventricular septal defect (P = 0.0037) by single marker association analysis. In addition, a 20 kb haplotype composed of 27 SNPs correlated with ventricular septal defect (P = 0.05, multiple loci regression analyses based on reconstructed haplotype blocks). CONCLUSIONS: TBX5 is associated with the occurrence of ventricular septal defect and may be a predisposing gene to congenital heart disease in Han Chinese. This finding has set a direction for further genetic and functional studies.

Congenital vascular rings: a rare cause of respiratory distress in infants and children.

BACKGROUND: Congenital vascular rings may often cause unexplained respiratory symptoms in infants and young children. Their diagnosis and treatment are often delayed. Few studies of vascular rings have been reported in China. The aim of this study was to describe the clinical presentation, diagnosis and surgical management of infants and children with congenital vascular rings. METHODS: Clinical histories, physical examinations, investigations, image studies and surgical interventions were retrospectively evaluated in 7 children (age range: 2 months-4 years, mean 7 months) with congenital vascular rings. Chest radiography was performed in all patients. Echocardiography and computed tomography (CT) with 3-dimensional (3D) reconstructions were performed in 6 patients. Esophagography, cardiac catheterization and angiography, and bronchoscopy were performed in 1, 1 and 4 children, respectively. RESULTS: Six of the 7 patients had respiratory symptoms, including recurrent cough, stridor and wheeze. Age at onset of symptoms ranged from 1 month to 11 months. Chest X-ray showed nothing important on the vascular rings, besides bronchitis and pneumonia. Contrast-enhanced CT diagnosed vascular rings in 6 patients. Four patients had double aortic arches, two had balanced arches and two were right arch dominant. One patient had a right aortic arch with left ligament and 1 patient had a pulmonary artery sling. Echocardiography failed to diagnose vascular rings in 2 patients. The esophagogram of 1 patient showed esophageal compression. Bronchoscopy of 4 patients showed compression of the distal trachea. Five of the 7 patients underwent surgical division of the vascular rings. Surgical observation confirmed the CT findings in each patient. CONCLUSIONS: Patients, especially infants or young children, with recurrent respiratory symptoms such as chronic cough, stridor and wheeze, should be examined for the possible presence of congenital vascular rings. Contrast-enhanced CT can clearly show the anatomy of vascular rings. As a noninvasive technique, echocardiography is helpful for diagnosis. Early surgical management in symptomatic patients is effective.

[Clinical analysis of pediatric SARS cases in Beijing].

OBJECTIVE: To study clinical characteristics of pediatric SARS cases in Beijing. METHODS: Eighteen pediatric cases with SARS diagnosed on admission were analyzed. The cases were admitted to Beijing Children's Hospital and Ditan Hospital (pediatric ward) from April 8 to May 12. RESULTS: The 18 children aged 5 months to 15 years (10 male and 8 female) had epidemiologically linked findings. Fourteen cases had close contact with SARS patients. Four cases were living in the community where adult SARS patients were found. All the 18 patients but one presented with fever and cough. Most of them had high fever, 2 cases had bradycardia, 2 had diarrhea, and another 2 had tachypnea. Malaise and headache were noted only in 3 cases respectively which were much less frequently seen than in adult patients. Symptoms and signs of the children were much less severe and aggressive than adults cases. Thirteen children had chest radiographic consolidation. Of them, 9 cases had progressive changes after admission, then improved quickly. We did not find significant lower hemoglobin and platelet levels. Most patients had leukopenia and lymphopenia. Serologic test was performed for 15 cases and 8 were positive for SARS virus-IgG and 6 for IgM antibody. Of the 4 cases who had close contact with SARS adults and without chest radiograph abnormal findings, 3 were negative for SARS virus-antibodies. Part of the patients had temporary abnormality of myocardial enzyme and liver function. All these children finally had rapid improvement on chest radiograph. The patients were treated with antiviral agents and corticosteroid. Only two cases required oxygen therapy. No child needed assisted ventilation and no death, nor lung fibrosis occurred. After hospitalization, all patients were improved and discharged when this paper was being written. The average hospital stay of these patients was 14.6 days (6 - 22 days). CONCLUSION: Compared with adults, pediatric SARS patients seemed to have their own clinical characteristics. The disease in children had lower severity and infectivity than that in adults. The mechanisms of the disease in children should be studied in well-designed clinical trials. Cases like the 4 children who had close contact with SARS adult patients but without chest radiographic changes deserve further studies with the help of more reliable and sensitive etiologic tests.