Mutations in the BEST1 gene are associated with a range of retinal diseases collectively referred to as "Best diseases", including Best vitelline macular dystrophy. More than 300 mutations at different sites of the BEST1 gene have been found, which may cause a series of functional disorders such as the mistransport of the calcium-activated anion channel protein-1 protein encoded by it, protein oligomerization defects, and abnormal anion channel activity, leading to different clinical phenotypes. Although it has been established that the BEST1 gene mutation is associated with at least one different type of Best disease, the relationship between the specific gene mutation site and the specific clinical phenotype has not been fully defined. For the time being. Drugs and gene therapy for the Best diseases are still in the basic research stage, which provides a broad development space for future treatment exploration. In the future, when selecting gene therapy in clinical applications, it is necessary to combine the clinical phenotype and molecular diagnosis of patients, and clearly define their mutation types and pathogenic mechanisms in order to achieve better personalized treatment effects.
Tyrosine kinase inhibitors (TKIs) are the standard of care for non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation. The efficacy of TKIs and prognosis of EGFR-mutated patients with compound EGFR mutation, oncogene mutation, suppresser gene mutation or other diver gene mutation are worse than those of patients with a single EGFR mutation. This article makes a review of related clinical researches aiming to provide references for clinical scenarios. To sum up, molecular alterations and clinical features should be correlated as accurately and dynamically as possible in the diagnostic and therapeutic process, and combined therapeutic strategies should be chosen flexibly and reasonably to improve patients’ survival and prognosis.
Objective To investigate the spectrum of mitochondrial DNA (mtDNA) mutations in Chinese patients with Leber′s hereditary optic neuropathy (LHON). Methods The primary mtDNA mutations (G3460A、G11778A and T14484 C) of 140 patients with LHON were detected by mutation-specific priming polymerase chain reaction (MSP-PCR), heteroduplex-single strand conformation polymorphism polymerase chain reaction (HA-SSCP), restriction fragment length polymorphisms (RFLP) and measurement of DNA sequence. The transmissibility of the patients′ stirps was analyzed.Results In the 140 patients with LHON, G11778A mtDNA primary mutation was found in 130 (92.9%), including 113 males and 17 females; G3460A mutation was found in 2 (1.4%) including 1 male and 1 female; G14484A mutation was found in 8 (5.7% ) including 6 males and 2 females.Conclusion In Chinese patients with LHON, the incidence of G11778A mtDNA mutation is higher than that of G3460A and T14484C. (Chin J Ocul Fundus Dis，2003，19：269-332)
ObjectiveTo summarize the research progress of KRAS mutation in pancreatic tumorigenesis and therapy.MethodThe research progress of KRAS mutation in pancreatic tumorigenesis and therapy were summarized by reading the domestic and international literatures published in recent years.ResultsPancreatic cancer had the title of " king of cancer”. More than 90% of pancreatic cancer patients had KRAS mutation. KRAS had a complex relationship with pancreatic cancer through downstream signaling pathways, including Raf (rapidly accelerated fibrosarcoma)-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK), phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)-protein kinase B (AKT), and RalGDS-Ral. Although basic research on pancreatic cancer was deepening, there was still a lack of effective molecular targeted drugs.ConclusionsKRASgene plays an important role in the occurrence of pancreatic cancer. The treatment associated with KRAS mutation provides a more effective prognostic possibility for pancreatic cancer patients.
ObjectiveTo investigate the predicting effect of PIK3CA mutations for the efficacy and prognosis of hepatocellular carcinoma (HCC) patients received surgical resection. MethodsPCR and DNA sequencing were used to detect the PIK3CA mutation status of 79 HCC tissues, its impact on the short and long term effects of the patients were analyzed. ResultsIn this group of patients, mutation rate of PIK3CA gene exon 9 was 39.24% (31/79), PIK3CA mutation rate correlated with lymph node status and tumor differentiation (P < 0.05). The therapeutic effect of patients with PIK3CA mutation was significantly poor than that of the non-mutated group (P < 0.05). The three-year cumulative survival of patients with PIK3CA mutation (33.33%) was significantly lower than non-mutated group's (60.00%) by Kaplan-Meier (P < 0.05). ConclusionPIK3CA gene mutation in exon 9 could impact the efficiency of surgical resection in patients with HCC and could predict a poor survival prognosis.
Objective To research the clinical characteristics and the arysulfatase A(ARSA) gene screening inafamily withametachromatic leukodystrophy and epilepsy child. Methods Clinical data were collected and ARSA gene were tested by PCR and Sanger sequencing in the pedigree． Results Two mutations in exon 2 of ARSA gene was identified in the proband includingaknown heterozygous missense mutation c.293C>T which was also found in his mother andanovel frameshift mutation c.302de1G. None of them was found in the proband’s brother. Conclusion The intractable epilepsy of the proband was related to his metachromatic leukodystrophy. Andanew frameshift mutation c.302delG was found in his ARSA gene, which haven’t reported around the world yet. Combined with the patient’s typical late infantile presentation, we speculated that the frameshift mutation c.302delG may be the cause of MLD.
Objective To detective KRAS and BRAF mutations in gastrointestinal stromal tumors (GISTs) and explore its significance in resistance of imatinib treatment. Methods Three hundred and eighty-one c-kit/PDGFRA mutation samples, 119 c-kit/PDGFRA wild type samples, and 19 pairs of samples before and after imatinib resistance from 519 patients with GIST were enrolled in this study. Polymerase chain reaction was used to detect KRAS exon 2 and BRAF exon 15 mutations. The survival data were evaluated in patients with KRAS or BRAF mutation. Results KRAS mutation was found in 2 cases (1.7%) of c-kit /PDGFRA wild type GISTs, the type of KRAS mutation was G12D and G12C, respectively. BRAFV600E mutation was found in 2 cases (1.7%) of wild type GISTs. No KRAS and BRAF mutations were found in the patients with the c-kit/PDGFRA mutation GISTs and pairs of GISTs before and after imatinib resistance. Two patients with KRAS mutation showed shorter progression free survivals for imatinib treatment. Two patients with BRAF mutation had longer recurrence free survivals. Conclusions Low frequency of KRAS or BRAF mutation only happens in wild type GISTs. KRAS mutation might be related to imatinib primary resistance, but not to secondary resistance.
Objective To study the mutations at 1 573 fragment of TNF receptor II (TNFR-II) gene in patients with keloid. Methods The tissue DNA was extracted from 22 samples of keloids donated by 22 patients (6 males and 16 females, aged 18-53 years), and all keloids were examined and classified by pathologist. The peri pheral blood DNA was extracted from the same patients as the control. PCR was used to ampl ify the 1 573 fragment of TNFR-II gene from the keloid tissue DNA and peripheral blood DNA. The PCR products were sequenced directly and then compared with the GeneBankdata. Results All the concentration of the extracted DNA in trial were higher than 0.50 μg/μL and the purity (A260/A280) ofthe extracted DNA were higher than 1.5. It closed to the magnitude of the design DNA fragment by agarose gel electrophoresis examining, and corresponded with the test requirement. Mutations at 1 573 fragment of TNFR-II gene were detected in 13 out of 22 keloids. The mutation incidence was 59.1%. Among them, 9 had point mutation at codon 1 663, accounting 40.9%. No TNFR-II gene mutation was detected in all peripheral blood samples. There were significant difference between keloids DNA and peripheral blood DNA (P lt;0.01). The mutations involved point mutation, deletion and insertion as well as multisite and multitype. Conclusion There is a correlation between the mutation at 1 573 fragment of TNFR-II gene and keloid.
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 detect and analyse the mutations in rhodopsin gene of members in a family affected by autosomal dominant retinitis pigmentosa (ADRP). Methods Using the polymerase chain reaction (PCR), we amplified exon 1-5 of rhodopsin gene in patients with ADRP,and analyzed it with direct sequence measuement. Results The Gly-182-Asp mutation in the rhodopsin gene was detected in most of affected members of this ADRP family, but no mutation was detected in two affected members and the control ones. Conclusion We cannot regard the Gly-182-Asp mutation in the rhodopsin gene as the pathagenic factor of the ADRP family. It is likely there is a new gene next to the rhodopsin gene. (Chin J Ocul Fundus Dis, 2002, 18: 256-258)