The pituitary gland is one of the basic endocrine organs of the body.The defect of certain transcription factors leads to abnormalities of embryonic organogenesis and differentiation failure of hormone-secreting cells,thus representing combined pituitary hormone deficiency(CPHD).The known transcription factors inducing CPHD include PROP1,HESX1,POU1F1,LHX3,LHX4 and others.Their impact on embryonic development through distinct ways results in various phenotypes.This review explains the pituitary embryonic development and the expression of the transcription factors mentioned above and their mutations responsible for CPHD.
To investigate the clinical and laboratory features of very long chain acyl-CoA dehydrogenase deficiency ( VLCADD ) and the correlations between its genotype and phenotype.Eleven patients diagnosed as VLCADD of Shanghai Jiaotong University School of Medicine seen from September 2006 to May 2014 were included. There were 9 boys and 2 girls, whose age was 2 d-17 years. Analysis was performed on clinical features, routine laboratory examination, and tandem mass spectrometry (MS-MS) , gas chromatography mass spectrometry (GC-MS) and genetic analysis were conducted.All cases had elevated levels of blood tetradecanoylcarnitine (C14:1) recognized as the characteristic biomarker for VLCADD. The eleven patients were classified into three groups: six cases in neonatal onset group, three in infancy onset group form patients and two in late onset group. Neonatal onset patients were characterized by hypoactivity, hypoglycemia shortly after birth. Infancy onset patients presented hepatomegaly and hypoglycemia in infancy. The two adolescent patients showed initial manifestations of exercise intolerance or rhabdomyolysis. Six of the eleven patients died at the age of 2-8 months, including four neonatal onset and two infant onset patients, with one or two null mutations. The other two neonatal onset patients were diagnosed since early birth through neonatal screening and their clinical manifestation are almost normal after treatments. Among 11 patients, seventeen different mutations in the ACADVL gene were identified, with a total mutation detection rate of 95.45% (21/22 alleles), including eleven reported mutations ( p. S22X, p. G43D, p. R511Q, p. W427X, p. A213T, p. C215R, p. G222R, p. R450H, p. R456H, c. 296-297delCA, c. 1605 + 1G > T) and six novel mutations (p. S72F, p. Q100X, p. M437T, p. D466Y, c. 1315delG insAC, IVS7 + 4 A > G). The p. R450H was the most frequent mutation identified in three alleles (13.63%, 3/22 alleles), followed by p. S22X and p. D466Y mutations which were detected in two alleles (9.09%, 2/22 alleles).The ACADVL gene mutations were heterozygous in our patients. The mortality of neonatal onset form and infant onset form is much higher than the late onset form patients, suggesting a certain correlation between the genotype and phenotype was found. The earlier diagnosis and treatment of VLCADD are of vital importance for the improvement of the prognosis of the patients.
Objectives To investigate the clinical and laboratory features of neonatal intrahepatic cholestasis caused by citrin deficiency(NICCD).Methods Twelve patients with idiopathic intrahepatic cholestasis and jaundice were included in our study.Diagnosis was made by routine laboratory examination,tandem mass spectrometry(MS-MS)and gas chromatography mass spectrometry(GC-MS)analysis.Clinical features,blood amino acid and acylcarnitine profiles,urinary organic profiles and other laboratory tests were analyzed.Results NICCD patients showed low birth weight.Laboratory data suggested increased γ-GT,ALP,and α-fetoprotein,prolongation of the prothrombin time,hyperbilirubinemia,and hypoproteinemia.Six patients had obvious hypoglycemia,3 had mild hyperammoniemia.Only 1 showed hypergalactosemia.Liver pathological analysis of 3 patients indicated intrahepatic cholestasis and hepatocyte steatosis.MS-MS analysis of the blood sample revealed distinctive elevation of citrulline,methionine,threonine,tyrosine and elevation of free carnitine,C2-carnitine,C3-carnitine and long-chain acylcarnitines.GC-MS analysis of urine samples showed elevated 4-hydroxyl phenyllactic acid,4-hydroxyl phenylphruvic acid and 4-hydroxyl phenylacetic acid.Conclusions Differential diagnosis of cholestatic jaundice of unknown origin in infants should include NICCD.It is important to perform MS-MS in early neonatal time to identify infants with neonatal intrahepatic cholestasis caused by citrin deficiency.
Objective To obtain the mutation spectrum of glucose-6-phosphatase (G6Pase) gene in Chinese patients with glycogen storage disease type Ⅰa (GSDⅠa) and to analyze the relationship of its genotype and phenotype. Methods Genomic DNA samples were extracted from peripheral blood of 21 GSDⅠa patients from 19 families, their parents and 21 normal individuals. Five exons of G6Pase gene were analyzed in patients by PCR, direct DNA sequencing, family analysis and restriction enzyme analysis. Results The most prevalent mutation was 727G→T, accounting for 34 (80.95%) of 42 alleles examined, followed by R83H mutation, which accounted for 4 (9.52%) mutant alleles. Three other mutations, R170X, Q104X, 341delG were identified. Thirteen patients were homozygotes for 727G→T. Eight patients were heterozygotes for 727G→T. The 727G→T and R83H mutations were also confirmed by restriction enzyme analysis. The 653A→G homozygous transition was found in all the 21 patients, 33 parents of patients and 21 normal individuals. From clinical and biochemical aspects, the phenotypic heterogeneity was observed in the patients with the same genotype. Hepatic adenoma was detected in 1 patient of 727G→T homozygote. Conclusion A screening for the 727G→T and R83H mutations by DNA-based diagnostic methods can detect 90% of the G6Pase mutant alleles in Chinese patients with GSDⅠa. Combined with clinical and biochemical characters, the noninvasive molecular diagnosis for GSDⅠa may ultimately replace the conventional means of enzymatic diagnosis that requires liver biopsy.
Objective To analyse the concentrations of 21 elements in 24 h urine of patients with Wilson's disease(WD) during penicillamine therapy. Methods Forty patients with WD undergoing penicillamine therapy and hypo-copper diets were collected(WD group),and another 12 healthy people were served as control group.The concentrations of 21 elements of Cr,Fe,Co,Se,Mn,Cu,Zn,As,Be,Al,V,Ni,Cd,Sb,Ba,Pb,Ti,Th,U,Ca and Mg in 24 h urine were determined by inductively coupled plasma mass spectrometry. Results For 7 essential trace elements(Cr,Fe,Co,Se,Mn,Cu and Zn),the concentrations of Mn,Cu and Zn in 24 h urine of WD group were significantly higher than those in control group(P0.05,P0.01 and P0.01).For 12 unessential trace elements(As,Be,Al,V,Ni,Cd,Sb,Ba,Pb,Ti,Th and U),the concentration of As in 24 h urine of WD group was significantly higher than that in control group(P0.05).For 2 macroelements(Ca and Mg),the concentration of Ca in 24 h urine of WD group was significantly higher than that in control group(P0.001). Conclusion For patients with WD undergoing penicillamine therapy and hypo-copper diets,the concentration of Cu in 24 h urine increases,and those of Mn,Zn,As and Ca also change.
It was found that the isoniazid could electrocatalytically reduce the dissolving oxygen to form the active oxygen-based species at the Hg film modified electrode.Then,based on the sensitive CL response performances of active oxygen-based species to luminol CL reaction system,a new and high sensitive ECL method for the determination of isoniazid was developed.Under the optimum experimental conditions,the calibration graphs are linear over the range 2.0×10-9 to 2.0×10-6 g/mL for isoniazid.The detection limit was 6.7×10-10 g/mL.The proposed method was successfully used to determine isoniazid in pharmaceutical formulations.
Objective To study the effect of high phenylalanine on Nogo A mRNA and protein expression of oligodendrocyte(OLG).Methods OLG precurosor cells were induced to OLG.Real-time PCR and Western blot were used to evaluate the mRNA and protein expressions of Nogo A,respectively.The identification and location were performed by immunohistochemistry and immunofluorescence.In the condition of high phenylalanine(0.9 μmol/L),the mRNA and protein expressions of Nogo A at 0(control),12,24 and 48 h was detected by real-time fluorescent quantitative PCR and Western blot.Results Compared with the OLG without high phenylalanine,the mRNA level of Nogo A in the groups with high phenylalanine for 12,24 and 48 h were slightly up-regulated,with the ratio of 0.98,1.09 and 1.20,respectively.The protein level of Nogo A in the groups with high phenylalanine for 12,24 and 48 h was up-regulated significantly,with 1.5,5.3 and 6.7 times to the control group.Conclusion The expression of Nogo A was up-regulated in the condition of high phenylalanine,which might be involved in the etiology of phenylketonuria.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)