Analysis of FGD1 gene variant in a child with Aarskog-Scott syndrome / 中华医学遗传学杂志

OBJECTIVE@#To detect pathogenic variant of the FGD1 gene in a boy with Aarskog-Scott syndrome.@*METHODS@#Genetic variant was detected by high-throughput sequencing. Suspected variant was verified by Sanger sequencing. The nature and impact of the candidate variant were predicted by bioinformatic analysis.@*RESULTS@#The child was found to harbor a novel c.1906C>T hemizygous variant of the FGD1 gene, which has led to conversion of Arginine to Tryptophane at codon 636(p.Arg636Trp). The same variant was found in his mother but not father. Based on the American College of Medical Genetics and Genomics guidelines, the c.1906C>T variant of FGD1 gene was predicted to be likely pathogenic(PM1+PM2+PM5+PP2+PP3+PP4).@*CONCLUSION@#The novel c.1906C>T variant of the FGD1 gene may underlay the Aarskog-Scott syndrome in this child. Above finding has enabled diagnosis for the boy.

Gene mutations in 32 family with phenylketonuria / 中华实用儿科临床杂志

Objective By detecting the mutations spectrum of phenylalanine hydroxylase(PAH)gene in phe-nylketonuria(PKU)patients and their parents. The researchers analyzed the gene mutation features and high - frequency mutations and determined the relationship between the genotype and the phenotype,which would provide a theoretical basis for the early diagnosis and genetic consultation of PKU children in the region. Methods In this study,13 exons and their flanking introns of the PAH gene in 32 PKU patients and their parents from Wuxi and Suqian in Jiangsu province were sequenced by using the next - generation sequencing(NGS)technology. Results Sixty - one mutant sites and 32 mutant genes were detected in 32 PKU patients,and the mutation detection rate was 95. 31%(61 / 64 cases). The variants at c. 721C ﹥ T,c. 1068C ﹥ A,c. 611A ﹥ G,c. 1197A ﹥ T,c. 728G ﹥ A,c. 331C ﹥ T and c. 442 -1G ﹥ A were common mutations in the region with mutation frequency over 5% . What's more,4 novel variants of c. 699C ﹥ G,c. 265C ﹥ T,c. 722G ﹥ A and c. 1194A ﹥ G were found. Of those,c. 699C ﹥ G was not recorded in the PAH variant database and HGMD database and. c. 265C ﹥ T,c. 722G ﹥ A,and c. 1194A ﹥ G were first reported in the Chi-nese population. Genotype - accurate biochemical phenotype correlation by using the Guldberg AV system revealed con-sistency rate of 38. 0%(8 / 21 cases),which the consistency rate between accurate biochemical phenotype and predic-tive phenotype of moderate to severe genotype was 92. 3%(12 / 13 cases),and mild genotype was 50. 0%(4 / 8 cases). Conclusions The PAH gene variants of PKU patients in Jiangsu province are distributed mainly in exons 7,of which the highest frequency gene mutation is c. 721 c ﹥ T. Moreover,one novel variant c. 699C ﹥ G was reported for the first time. The PKU children inherit the PAH mutation gene mainly from both parents. There are definite correlation between the genotypes and phenotypes.

Relationship between serum 25-hydroxy vitamin D3 concentration and obesity childhood / 中华实用儿科临床杂志

Objective To examine the relationship between the concentration of 25-hydroxy vitamin D3 [25-(OH) D3] in the serum and the body mass,the severity of obesity,body mass index(BMI),blood lipid,and their predicting role in obesity children.Methods The study recruited 244 subjects,who see the doctor in Wuxi Maternal and Child Health Hospital,Childhood Nutrition Outpatient from Jul.2011 to Feb.2013.The intake dose of vitamin D each day was investigated,and weight,height,BMI,concentration of 25-(OH) D3 in serum,and microelement were also measured.In addition,lipid metabolism of 38 cases with obesity over 3 years old was determined.Results 1.The serum 25-(OH) D3 concentration of obese children was (68.31 ± 23.06) nmol/L.The concentration of 25-(OH) D3 was lowest in the group of obese children over 36 months of age[(55.03 ± 15.18) nmol/L].2.The concentration of 25-(OH) D3 in the group of obese and overweight children was far lower than that of the children in the normal group (F =4.739,P ＜0.05).3.The concentrations of 25-(OH) D3 in the severely obese children was significantly lower than that of the mild and moderate obesity children(F =9.711,P ＜ 0.05).4.There were significantly inverse associations of serum 25-(OH) D3 with weight,weight and height percentage,BMI (r =-0.365,-0.237,-0.175,all P ＜ 0.001).5.There were significantly inverse associations between the concentration of 25-(OH) D3 in serum with weight,triglyceride in obese children more than 3 years old (r =0.476,-0.324,all P ＜ 0.05).Conclusions The decreasing level of 25-hydroxy vitamin D3 in the serum was associated with obesity.The cause of it might be the increase of the obese adipose tissue,vitamin D getting trapped in fat cells,and all these factors can lead to a less serum vitamin D levels.The vitamin D consumption of obese children is higher than that of normal children,and should supply more vitamin D to reach normal 25-(OH) D3 level.

Ca~(2+) signaling mediated salidrosides promotes directional differentiation of mouse bone marrow mesenchymal stem cells into nerve cells / 中国组织工程研究

BACKGROUND:Tranditional Chinese medicine,which possesses anti-oxidation properties,can promote directional differentiation of mouse bone marrow mesenchymal stem cells(BMMSCs)into nerve cells.Salidrosides,as the effective constituent of Rhodiola,have strong anti-oxidation function.OBJECTIVE:To investigate the molecule mechanism of salidrosides induced differentiation of mouse BMMSCs into nerve cells.METHODS:When in vitro cultured BMMSCs reached 80% confluency,the cells were assigned into 3 groups.Cells in the control group were cultured by complete culture medium;those in the induction and positive control groups were cultured by complete culture medium adding 20 mg/L salidrosides or 0.1 mg/L nerve growth factors(NGF).The related gene and protein of nerve cells were detected using RT-PCR and Western blot method at 12 hours after culture.After that,the cells in the induction group were divided into 3 groups,the blocking agents EGTA(Ca~(2+) chelator),Nifedipine(L-type Ca~(2+) channel blocker)and LY294002(IP3 receptor blocking pharmacon)were applied to block the cellular Ca2* signal pathway respectively for 12 hours.RT-PCR and Western blot methods were used to study the signal transduction of the salidrosides.RESULTS AND CONCLUSION:①The expression of neuron specific enolase(NSE),B-Tubulin III,Nurri mRNA could be found ir the induction and positive control groups,instead of the control group;The expression abundance of the positive control group was smaller than that of the induction group.The expression abundance of GFAP mRNA was very low in each group,but the c-fos mRNA was expressed abundantly in the induction group.②Compared with the positive control group,the induction group could promote the NSE expression obviously,which was no expressed in the blank control group.?The expression of NSE and Nurri were conspicuously down-regulated when the Ecto Ca~(2+) and L-type Ca~(2+) channel and IP3 receptor were blocked respectively.Salidrosides can induce the differentiation BMMSCs into nerve cells. Ca~(2+) signaling and IP3 dependent Ca~(2+) signaling pathway play an important role in transduction salidrosides signal in BMMSCs differentiation.

Effects of Tri-ortho-cresyl Phosphate on Mitochondrial Membrane Permeability in Hen's Nerve Tissue / 环境与健康杂志

Objective To study the effects of tri-ortho-cresyl phosphate(TOCP) on mitochondrial membrane permeability in hen's nerve tissues and investigate the mechanism of the organophosphorus ester-induced delayed neurotoxicity(OPIDN).Methods Adult Roman hens were randomly divided into four groups,including three treated groups and one control group(24 in each group).The hens in the experimental groups were treated with TOCP by gavage at the single dosages of 185,375 and 750 mg/kg respectively.TOCP was dissolved in corn oil and administered at 0.65 ml/kg.The control hens received an equivalent volume of corn oil by gavage.The hens were sacrificed on the 1st,5th,15th and 21st day after treatment and the cerebrum,cerebellum,spinal cord were dissected and homogenized in ice bath.The mitochondria in these nerve tissues were extracted to determine the changes of the membrane permeability and membrane potential.Results Compared with the control group,no significant increase of the mitochondrial membrane permeability in the cerebrum was observed in treated groups.In the cerebellum,the membrane permeability in the 185 mg/kg group had no significant changes,while in the 375 and 750 mg/kg groups it increased significantly on the 1st and 5th day after TOCP treatment(P