Genetic epilepsy with febrile seizures plus (GEFS+) is a new type of genetic epilepsy syndrome with a marked hereditary tendency. Febrile seizure is the most common clinical symptom, followed by febrile seizure plus, and with/without absence seizures, focal seizures, and generalized tonic-clonic seizures. Results of the polymerase chain reaction (PCR), exon sequencing and single nucleotide polymorphism (SNP) analysis showed that the occurrence of GEFS+ is mainly related to the mutation of gamma aminobutyric acid type A receptor gamma 2 subunit (GABRG2), but its pathogenesis was still unclear. The main types of GABRG2 mutations include missense mutation, nonsense mutation, frameshift mutation, point mutation and splice site mutation. All these types of mutations can reduce the function of ion channels on cell membrane, but the degree and mechanism of dysfunction are different, which may be the main mechanism of epilepsy. This article will focus on the relationship between GEFS+ and the mutation types of GABRG2 in recent years, which is of great significance for clinical accurate diagnosis, anti-epileptic treatment strategy and new drug development.
The loss of heterozygosity and mutation for nm23-H1 gene in colorectal carcinomas were studied by Southern blot and RT-PCR-SSCP/silver staining sequencing. The rate of loss of heterozygosity for nm23-H1 was 29.63%. The cases of Duke’s stage D and distant metastatsis had higher frequency of the loss of heterozygosity. No mutation for nm23-H1 was found in colorectal carcinomas. These reaults indicate that the loss of heterozygosity for nm23-H1 may play a significant role in the malignant progression and distant metastasis in colorectal carcinomas.
ObjectiveTo explore the relationship of the clinicopathological characteristics of non-small cell lung cancer (NSCLC) with the mutations of epidermal growth factor receptor (EGFR), K-ras and EML4-ALK fusion gene in cell blocks of pleural effusion (PLE). MethodsA total of 268 cytological specimens of PLE (pleural effusion), from Central Hospital of Zibo city were collected from advanced NSCLC patients between January 2012 year and June 2014 year. There were 165 male and 103 female patients at age of 53.6 (31-76) years. Qualitative diagnosis has been made in the 268 patients using PLE samples with conventional smear. Immunohistochemical staining combined with cell block section were used for further classification. There were 76 patients diagnosed as NSCLC with 39 patients of adenocarcinoma and 37 patients of squamous-cell carcinoma. In the 76 patients of lung biopsy specimens and PLE, EGFR and K-ras mutations, EML4-ALK fusions were tested. ResultsEGFR mutations rate was 34.21% (26/76). K-ras mutations rate was 6.58% (5/76). EML4-ALK fusions rate was 7.89% (6/76) at the same time. EGFR and K-ras mutations, EML4-ALK fusions were mostly found in young female adenocarcinoma patients who were non-smokers. EGFR and K-ras mutations or EML4-ALK fusions were not found in the same patient. ConclusionCytological specimens are feasible for detecting EGFR were K-ras mutations and EML4-ALK fusions. This will especially benefit to patients whose histological specimen can not be obtained.
Objective To study the basic and clinical achievements in diagnosis and therapy of hereditary pancreatitis. Methods Related literatures of recent years were reviewed. Results Hereditary pancreatitis was a rare type of pancreatitis, with an estimated penetrance of 80%, and was believed to be caused by a mutation in the cationic trypsinogen gene. Patients with hereditary pancreatitis had a high frequency of pancreatic cancer.Conclusion The progress has been made on hereditary pancreatitis and has given us many useful suggestions for a better understanding about this difficult medical problem.
Lung cancer in never-smokers has been identified as a separate disease entity. Notably, the proportion of this distinct disease has been reported to increase in recent decades. Due to its occult onset and lack of clinical specificity, patients with this disease are always diagnosed with advanced stage. This review summarizes the current literatures about the risk factors, clinicopathological characteristics, molecular features, and prognosis of lung cancer in never-smokers, which will enhance our understanding and facilitate the precise management of this distinct disease.
ObjectiveTo observe the mutation and expression of Nkx2.5 in congenital heart disease patients with diminutive pulmonary blood. We preliminarily explored the association between Nkx2.5 gene and pathogenesis of congenital heart disease patients with diminutive pulmonary blood. MethodsFifty six patients of congenital heart disease with diminutive pulmonary blood in the first affiliated hospital of Bengbu medical college and Anhui province children, s hospital between May 2012 and May 2014 were as an experimental group. Sixty three patients of ventricular septal defect were as a control group. In the trial group, there were 30 males and 26 females averagely aged 5.82± 4.23 years ranking from 6 months to 14 years. In the control group, there were 36 males and 27 females averagely aged 6.93± 4.56 years ranking from 6 months to 14 years. Before operation, peripheral venous blood of all the patients were collected. We used polymerase chain reaction combined with DNA sequencing technology to detect Nkx2.5 gene exon sequence and to analyze the association between Nkx2.5 gene mutation and congenital heart disease with diminutive pulmonary blood. And we got some hypertrophic myocardial tissue from right ventricular outflow tract in the operation, whose size was 0.5× 0.5× 0.5 cubic centimeter. And we extracted myocardial tissue RNA. The expression changes of Nkx2.5 gene mRNA were detected by real-time fluorescence quantitative polymerase chain reaction technique. ResultsThere was no mutations tested out in the peripheral venous blood in both two groups. The expression of mRNA in Nkx2.5 gene of the trial group was lower than that in the control group with a statistical difference. ConclusionNkx2.5 gene mutation may be associated with multiple factors. The occurrence of congenital heart disease with diminutive pulmonary blood may be related with a decline of Nkx2.5 gene expression in the myocardial tissue.
Objective To systematically review the association between prothrombin gene G20210A mutation and the risk of cerebral venous thrombosis (CVT). Methods Databases including PubMed, Springer, Google Scholar, The Cochrane Library (Issue 1, 2016), CNKI, WanFang Data and CBM were searched for case-control studies concerning the association between prothrombin gene G20210A mutation and cerebral venous thrombosis risk from inception to January 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software and Stata 12.0 software. Results A total of 26 case-control studies were included, involving 1 361 CVT cases and 6 323 controls. The results of meta-analysis showed that: there was a significant association between prothrombin gene G20210A mutation and CVT risk (OR=4.56, 95% CI 3.51 to 5.93,P<0.000 01). Sensitivity analysis showed no significant publication bias was detected confirmed the stability of results. Subgroup analysis showed that G20210A mutation increased CVT risk in adults (OR=5.02, 95% CI 3.81 to 6.60,P<0.000 01), but not in children (OR=1.99, 95% CI 0.83 to 4.79,P=0.12). Conclusion Prothrombin gene G20210A mutation can significantly increase the CVT risk. Due to the limited quality and quantity of included studies, the above results are needed to be validated by more high quality studies.
ObjectiveTo explore the action of dominant-negative effect on mutant insulin gene-induced diabetes.Methods293T cells were transfected with a recombinant plasmid containing mutant preproinsulinogen complementary DNA (cDNA) and a recombinant plasmid containing human wild-type preproinsulinogen cDNA. There were 5 mutant groups which mutant preproinsulins respectively bear substitutions V(A3)L, C(A7)Y, R(SP6)H, G(B8)S or G(C28)R. Wild-type mouse preproinsulin and wild-type human preproinsulin were co-transfected as normal control group. After 48 hours, medium and cells were collected. Human proinsulin were detected by human-specific proinsulin radioimmunoassay.ResultsCompared with the control group [(135.84±1.89) pmol/L], human proinsulin levels in medium of C(A7)Y group [(29.28±6.85) pmol/L] and G(B8)S group[(33.62±10.52) pmol/L] decreased significantly (P<0.01). There was no significant difference in human proinsulin level between the other groups and the control group (P>0.05).ConclusionMutants C(A7)Y and G(B8)S induce the dominant-negative effect on co-existing wild-type proinsulin.
ObjectiveTo investigate the relationship of concomitant BRAFV600E gene mutation with the predictive factors of papillay thyroid microcarcinoma(PTMC). MethodsBy fluorescence quantitative PCR method to detect BRAFV600E gene mutation of PTMC of 86 cases, and to detect the relationship with clinical pathological features of PTMC by single factor and multi-factor logistic regression analysis. ResultsThe morbidity of BRAFV600E gene mutation was 65.1%(56/86). By univariate analysis, BRAFV600E gene mutation status showed a related trend with lymph node metastasis(P=0.057). The multivariate analysis showwd that lymph node metastasis was correlated with BRAF V600E gene mutation(P < 0.05). When the diameter of tumor > 5 mm and≤10mm, BRAFV600E gene mutation was no statistically significantly related to central lymph node metastasis(P > 0.05). When BRAFV600E gene mutations was negative in patients with tumor diameter≤5 mm, no lymph node metastasis sample appeared. ConclusionsThe presence of BRAFV600E gene mutation is an independent predictive factor for central lymph node metastasis. When PTC with preoperative BRAFV600E gene mutation positive, the central neck dissection should be routine performed. There should be re-examined the necessity of preventative central lymph node disection when the tumor diameter is 5 mm or less with the patients which mutation negative.
ObjectiveTo explore the correlation between expression of thyroid transcription factor-1 (TTF-1) and gene mutation of epidermal growth factor receptor (EGFR) in patients with resectable lung adenocarcinoma (LAC). Method Sixty-seven LAC patients who underwent surgical resection in the Department of Cardiothoracic Surgery of Shanghai No.6 Hospital and Department of Thoracic Surgery, Renji Hospital, School of Medicine of Shanghai Jiaotong University from June 2009 to December 2012 were enrolled in this study. There were 40 male and 27 female patients with their age of 37-79 (56.7±1.8) years. TTF-1 expression was detected by immunohistochemistry. EGFR gene mutation was examined with mutant-enriched polymerase chain reaction. The correlation between TTF-1 expression and EGFR gene mutation was analyzed with corrected chi-square test. ResultsAmong the 67 LAC samples, 57 samples were TTF-1 positive and 10 samples were TTF-1 negative. There was EGFR gene mutation in 44 samples. EGFR gene mutation rate was 73.7% (42/57) in TTF-1 positive patients and 20.0% (2/10) in TTF-1 negative patients. The sensitivity of TTF-1 expression to predict EGFR mutation was 95.5%, and the specificity was 34.8%. ConclusionEGFR gene mutation rate is higher in LAC patients with positive TTF-1 expression. Positive TTF-1 expression can be used to predict EGFR gene mutation in LAC patients.