Analysis of families with fetal congenital abnormalities but negative prenatal diagnosis by whole exome sequencing / 中华妇产科杂志

Objective:To evaluate the value of whole exome sequencing (WES) in prenatal clinical application.Methods:A total of 1 152 cases of congenital abnormal [including structural malformation, nuchal translucency (NT) thickening and intrauterine growth restriction] with traditional prenatal diagnosis [including G-band karyotype analysis and chromosome microarray analysis (CMA)] negative were analyzed. The congenital abnormal fetuses were divided into retrospective group and prospective group according to the time of WES detection, that is whether the pregnancy termination or not. According to the specific location of fetal malformation and their family history, the cohort was divided into subgroups. The clinical prognosis of all fetuses were followed up, and the effect of WES test results on pregnancy decision-making and clinical intervention were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in the third trimester or after birth were re-analyzed.Results:Among 1 152 families who received WES, 5 families were excluded because of nonbiological parents. Among the remaining 1 147 families, 152 fetuses obtained positive diagnosis (13.3%,152/1 147), including 74 fetuses in the retrospective group (16.1%,74/460) and 78 fetuses in the prospective group (11.4%,78/687). In fetuses with negative CMA and G-band karyotype analysis results but new phenotypes in the third trimester or after birth, the positive rate by WES data re-analysis was 4.9% (8/163). A total of 34 (21.3%, 34/160) fetuses were directly affected by the corresponding positive molecular diagnosis. Among 68 cases of live births with diagnostic variation grade 4, 29 cases (42.7%, 29/68) received appropriate medical intervention through rapid review of WES results.Conclusions:WES could increase the detection rate of abnormal fetuses with negative G-banding karyotype analysis and CMA by 13.3%. Prenatal WES could guide pregnancy decision-making and early clinical intervention. It might be an effective strategy to pay attention to the special follow-up of the third trimester and postnatal fetus and to re-analyze the WES data.

Application of whole exome sequencing technology in fetuses with congenital structural abnormalities / 中华医学遗传学杂志

OBJECTIVE@#To investigate the application value of whole exome sequencing technology in fetuses with congenital structural abnormalities.@*METHODS@#The chromosomal abnormalities of 1147 families were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in late pregnancy or after birth were reanalyzed. Subgroups were divided according to the organs involved and whether single malformation or not. The gene regulatory network map was drawn by using string database and Cytoscape software. Fisher exact probability method was used to compare the difference of the diagnostic rate of pathogenic genes among the groups.@*RESULTS@#A total of 160 fetal cases received positive molecular diagnosed, involving 178 variant sites of 125 pathogenic genes, including 8 cases (4.9%, 8/163) by data reanalysis, and the overall positive diagnosis rate was 13.9%. Diagnostic rate was highest in the group of skeletal malformation (31.5%, 39/124) and lowest in that with thoracic malformation (0, 0/32). The gene clusters of fetal edema and intrauterine growth restriction were independent, and were not associated with the major structural malformations. The probability of each parent carrying the same recessive gene variant was 0.03 (39/1146) and 0.08 (4/53) with positive family history.@*CONCLUSION@#For fetuses with congenital structural abnormalities that are negative for conventional genetic tests, 13.9% of phenotypic associated pathogenic/likely pathogenic genetic variants can be detected by whole exome sequencing technology. Its application value for prenatal diagnosis varies in fetus with different organs involved. Reanalysis of sequencing data for cases with new phenotypes in late pregnancy or after birth can further improve the molecular diagnosis rate. Further investigations are needed to explore the related genetic mechanisms.

Correlation between fatty acid receptor GPR120 and glucose transporter 4 / 中国免疫学杂志

Objective:To investigate the correlation between G protein-coupled receptor 120 ( GPR120 ) and glucose transporter 4 (GLUT4) in 3T3-L1 cells.Methods:3T3-l1 cells were induced for differentiation,GRP120 mRNA was detected by RT-PCR and Oil red O was used to determine fat expression.GPR120 expression was knocked down by a specific siRNA in 3T3-L1cells.3T3-L1 cell that were tranfected with GPR120 siRNA were incubated with palmitic acid for 24 hours.Then,real-time PCR and Western blot were used to detect the expression of GLUT4 mRNA and protein.Results: Induced differentiation led to GPR120 overexpression in 3T3-L1 cells ( P<0.05 ).GPR120 knockdown resulted in reduction of both lipid volume and number in 3T3-L1 cells.Furthermore,GPR120 knockdown decreased GLUT4 mRNA and protein levels in 3T3-L1 cells (P<0.05,respectively).Conclusion:GPR120 affects the expression level of GLUT4 in insulin signaling pathway,suggesting its involvement in the initiation of insulin resist-ance.

Analysis of the death cause of children less than 5 years old in Huishan district of Wuxi / 中国基层医药

Objective To analyze the death cause of children less than 5 years old in Huishan district of Wuxi,in order to reduce the mortality of children under 5 years of age and put forward effective intervention measures.Methods According to “monitoring project of children below 5 years old died in Jiangsu Province”,the death surveillance data of this area of children below 5 years old were analyzed.Results The mortality of children under 5 years of age in Huishan district from 2001 to 2010 was 6.87‰,infant mortality was 5.06‰,the neonatal mortality was 3.75‰ and early neonatal mortality rate was 2.66‰.Death cause of children under 5 years old,the 5 cis-position were accident,premature and low birth weight,congenital malformation,congenital heart disease,birth asphyxia.Conclusion The death of children under 5 years old in Huishan area decreased,accidental injury,premature and low birth weight were the main causes of death.To reduce the mortality of children under 5 years old,should strengthen the safety education,reduce the accident,vigorously promote the pre-marital medical examination,strengthen health care and supervision in pregnancy,reduce the birth defect,improve obstetric,pediatric medical quality and medical technology.

Association between nitrotyrosine and coronary heart disease in type 2 diabetes / 中国综合临床

Objective To investigate the association of nitrotyrosine with coronary heart disease (CHD) in type 2 diabetes mellitus.Methods The nitrotyrosine levels were determined in 109 patients of type 2 diabetes mellitus without CHD (T2DM).One hundred and fifty-two patients of type 2 diabetes mellitus with CHD (T2DM-CHD) and 103 healthy control subjects by ELISA.Results T2DM-CHD patients had significantly increased nitrotyrosine compared with T2DM group and the control group [ ( 78.17±10.68 )nmol/L,(70.50 ± 9.13) nmol/L vs ( 63.23 ± 11.55 ) nmol/L,Ps ＜ 0.01 ].Nitrotyrosine was correlated with total cholesterol,triglyceride,fasting glucose and Gensini Score (r=0.361,P=0.009;r =0.206,P=0.001 ;r=0.347,P=0.026; r=0.466,P ＜ 0.001 ).Multivariable logistic regression showed nitrotyrosine was independently associated with CHD combined with type 2 diabetes mellitus ( OR=1.094,95％ CI:1.053-1.137 ; P ＜ 0.01 ).Conclusion Nitrotyrosine plays an important role in the formation and development of cardiovascular disease in tvoe 2 diabetes.