Objective:To study the role of the mutations of p53, APC and K-ras genes in 47 cases of 3 types of intestinal metaplasia (IM) of gastric mucosa. Methods:In 47 cases of IM, exons 5- 8 of p53 and exons 15 of APC were ex...Objective:To study the role of the mutations of p53, APC and K-ras genes in 47 cases of 3 types of intestinal metaplasia (IM) of gastric mucosa. Methods:In 47 cases of IM, exons 5- 8 of p53 and exons 15 of APC were examined with PCR-SSCP and codon 12 of K-ras with PCR-RFLP to detect the existence of any mutations of these structures. Results:Muta- tions of p53, APC and K-ras were found in 29.8% (14/47),6.4% (3/47) and 6.4% (3/47) respectively in our series of patients who consisted of 33 with types I and II and 14 with type III of IM. The mutation rate of p53 was far higher in patients with type III IM (57.1%,8/14) than in those with types I and II IM(18.2%,6/33)(P <0.05). Though the mutation rate of APC and K-ras was also higher in the patients with type III IM than in those with types I and II IM, it was of no statistical significance (P >0.05). In one case of type III IM, mutation of both p53 and K-ras was found. Conclusion: The molecular changes of 3 types of IM are different. The mutation of p53 may be closely related to carcinogenesis in cases of type III IM and it serve as a sign for the early diagnosis of gastric carcinoma.展开更多
BACKGROUND Patients harboring gene mutations like KRAS,NRAS,and BRAF demonstrate highly variable responses to chemotherapy,posing challenges for treatment optimization.Multiparametric magnetic resonance imaging(MRI),w...BACKGROUND Patients harboring gene mutations like KRAS,NRAS,and BRAF demonstrate highly variable responses to chemotherapy,posing challenges for treatment optimization.Multiparametric magnetic resonance imaging(MRI),with its noninvasive capability to assess tumor characteristics in detail,has shown promise in evaluating treatment response and predicting therapeutic outcomes.This technology holds potential for guiding personalized treatment strategies tailored to individual patient profiles,enhancing the precision and effectiveness of colorectal cancer care.AIM To create a multiparametric MRI-based predictive model for assessing chemotherapy efficacy in colorectal cancer patients with gene mutations.METHODS This retrospective study was conducted in a tertiary hospital,analyzing 157 colorectal cancer patients with gene mutations treated between August 2022 and December 2023.Based on chemotherapy outcomes,the patients were categorized into favorable(n=60)and unfavorable(n=50)response groups.Univariate and multivariate logistic regression analyses were performed to identify independent predictors of chemotherapy efficacy.A predictive nomogram was constructed using significant variables,and its performance was assessed using the area under the receiver operating characteristic curve(AUC)in both training and validation sets.RESULTS Univariate analysis identified that tumor differentiation,T2 signal intensity ratio,tumor-to-anal margin distance,and MRI-detected lymph node metastasis as significantly associated with chemotherapy response(P<0.05).Multivariate Logistics regression confirmed these four parameters as independent predictors.The predictive model demonstrated strong discrimination,with an AUC of 0.938(sensitivity:86%;specificity:92%)in the training set,and 0.942(sensitivity:100%;specificity:83%)in the validation set.CONCLUSION We established and validated a multiparametric MRI-based model for predicting chemotherapy response in colorectal cancer patients with gene mutations.This model holds promise for guiding individualized treatment strategies.展开更多
Objective:Keratoconus(KC)is a progressive corneal ectasia disorder,arising from a myriad of causes including genetic predispositions,environmental factors,biomechanical influences,and inflammatory reactions.This study...Objective:Keratoconus(KC)is a progressive corneal ectasia disorder,arising from a myriad of causes including genetic predispositions,environmental factors,biomechanical influences,and inflammatory reactions.This study aims to identify potential pathogenetic gene mutations in patients with sporadic KC in the Han Chinese population.Methods:Twenty-five patients with primary KC as well as 50 unrelated population matched healthy controls,were included in this study to identify potential pathogenic gene mutations among sporadic KC patients in the Han Chinese population.Sanger sequencing and whole-exome sequencing(WES)were used to analyze mutations in the zinc finger protein 469(ZNF469)gene.Bioinformatics analysis was conducted to explore the potential role of ZNF469 in KC pathogenesis.Results:Five novel heterozygous missense variants were identified in KC patients.Among them,2 compound heterozygous variants,c.8986G>C(p.E2996Q)with c.11765A>C(p.D3922A),and c.4423C>G(p.L1475V)with c.10633G>A(p.G3545R),were determined to be possible pathogenic factors for KC.Conclusion:Mutations in the ZNF469 gene may contribute to the development of KC in the Han Chinese population.These mutation sites may provide valuable information for future genetic screening of KC patients and their families.展开更多
AIM:To identify and assess mutations in the K-ras and BRAF genes in a cohort of Chinese patients with colorectal cancer (CRC) for their association with various clinicopathological parameters and prognosis.METHODS:Gen...AIM:To identify and assess mutations in the K-ras and BRAF genes in a cohort of Chinese patients with colorectal cancer (CRC) for their association with various clinicopathological parameters and prognosis.METHODS:Genomic DNA was isolated from frozen tissues.Pyrosequencing analysis was conducted to detect mutations in the K-ras (codons 12,13,and 61) and BRAF genes (codon 600).Statistical analysis was carried out using SPSS-15.0 software.RESULTS:Among the 118 colorectal cancer patients,we detected 41 (34.7%) mutations in the K-ras gene.Mutation frequencies at codon 12 and codon 13 were 23.7% (28/118) and 10.2% (12/118),respectively.Only one patient harbored a point mutation at codon 61 (0.8%,1/118).Gender was the only factor that showed an obvious relationship with K-ras gene mutation (female 44.7% vs male 28.2%,P=0.037).Other clinicopathological features,such as age,location of the tumor,tumor differentiation,Tumor,Node and Metastases classification,and the Union for International Cancer Control staging,showed no positive relationship with K-ras gene mutations.No significant correlation was observed between the presence of K-ras mutations (codons 12,13,and 61) and the survival of the patients.BRAF mutations were rare,and only two patients (1.7%) harbored a detectable mutation at codon 600.CONCLUSION:K-ras gene mutation is a common event in our 118 Chinese CRC patients,with an obvious relationship with gender.However,it seems not to be an independent prognostic factor in CRC patients.The BRAF gene is rarely mutated in Chinese CRC patients.展开更多
AIM:To study the genetic alteration in ACF and to define the possibility that ACF may be a very early morphological lesion with molecular changes,and to explore the relationship between ACF and colorectal adenoma even...AIM:To study the genetic alteration in ACF and to define the possibility that ACF may be a very early morphological lesion with molecular changes,and to explore the relationship between ACF and colorectal adenoma even carcinoma. METHODS: DNA from 35 CRC, 15 adenomas, 34 ACF and 10 normal mucus was isolated by means of microdissection. Direct gene sequencing of K-ras gene including codon 12, 13 and 61 as well as the mutation cluster region (MCR) of APC gene was performed. RESULTS: K-ras gene mutation frequency in ACF, adenoma and carcinoma was 17.6% (6/34), 13.3% (2/15), and 14.3% (5/35) respectively, showing no difference (P 】 0.05) in K-ras gene mutation among three pathologic procedures. The K-ras gene mutation in adenoma, carcinoma and 4 ACF restricted in codon 12 (GGT GAT), but the other 2 mutations from ACF located in codon 13 (GGC GAC). K-ras gene mutation was found more frequently in older patients and patients with polypoid cancer. No mutation in codon 61 was found in the three tissue types. Mutation rate of APC gene in adenoma and carcinoma was 22.9% (8/35) and 26.7% (4/15), which was higher than ACF (2.9%) (P 【0.05). APC gene mutation in carcinoma was not correlated with age of patients, location, size and differentiation of tumor. CONCLUSION: ACF might be a very early morphological lesion in the tumorogenesis of colorectal tumor. The morphological feature and gene mutation status was different in ACF and adenoma. ACF is possibly putative microadenoma that might be the precursor of adenoma. In addition, the development of a subgroup of colorectal carcinomas might undergo a way of normal epithelium ACF carcinomas .展开更多
AIM:To investigate the functions of promoter hypermethylation of O6-methylguanine-DNA methyltransferase(MGMT)gene in colorectal tumorigenesis and progression.METHODS:The promoter hypermethylation of MGMT gene was dete...AIM:To investigate the functions of promoter hypermethylation of O6-methylguanine-DNA methyltransferase(MGMT)gene in colorectal tumorigenesis and progression.METHODS:The promoter hypermethylation of MGMT gene was detected in 27 sporadic colorectal adenomas,62 sporadic colorectal carcinomas and 20 normal colorectal mucosa tissues by methylation-specific PCR.At the same time,the expression of MGMT protein was carried out in the same samples using immunohistochemistry.Mutantallele-specific amplification was used to detect K-rasG to A point mutation in codon 12.RESULTS:None of the normal colorectal mucosa tissues showed methylated bands.Promoter hypermethylation was detected in 40.7%(11 of 27)of adenomas and 43.5%(27 of 62)of carcinomas.MGMT proteins were expressed in nucleus and cytoplasm of normal colorectal mucosa tissues.Loss of MGMT expression was found in 22.2%(6 of 27)of adenomas and 45.2%(28 of 62)of carcinomas.The difference between them was significant(P=0.041).In the 6 adenomas and 28 carcinomas losing MGMT expression,5 and 24 cases presented methylation,respectively(P=0.027,P<0.001).Thirteen of the 19 colorectal tumors with K-rasG to A point mutation in codon 12 had methylated MGMT(P=0.011).The frequencies of K-rasG to A point mutation were 35.3%(12 of 34)and 12.7%(7 of 55)in tumors losing MGMT expression and with normal expression,respectively.CONCLUSION:Promoter hypermethylation and loss of expression of MGMT gene were common events in colorectal tumorigenesis,and loss of expression of MGMT occurs more frequently in carcinomas than in adenomas in sporadic patients.Hypermethylation of the CpG island of MGMT gene was associated with loss of MGMT expression and K-ras G to A point mutation in colorectal tumor.The frequency of K-ras G to A point mutation was increased in tumors losing MGMT expression.It suggests that epigenetic inactivation of MGMT plays an important role in colorectal neoplasia.展开更多
To evaluate the feasibility and clinical significance of the PCR SSP technique in detecting K ras gene mutation at codon 12 in pancreatic adenocarcinoma tissues. 80 specimens of surgical resection or biopsy samples ...To evaluate the feasibility and clinical significance of the PCR SSP technique in detecting K ras gene mutation at codon 12 in pancreatic adenocarcinoma tissues. 80 specimens of surgical resection or biopsy samples were tested at our hospital from January 1994 to September 1995. Three different special sequence primers (SSP) synthesized according to mutation styles of CGT, GTT, GAT were respectively prepared. Three amplification reactions were performed for each sample. The amplification products were analyzed by conventional polyacrylamide gel electrophoresis, stained with ethidium bromide and observed under UV transillumination. Results: All of the 34 pancreatic adenocarcinoma samples had positive PCR results with the mutation rate 100%. 7 cases were CGT mutation, 18 GGT and 17 GAT mutation, in which 2 types of mutation existed in 8 cases. No mutation appeared in 13 normal pancreatic tissues, 6 insulinomas, 6 chronic pancreatitis, 5 benign pancreatic cysts, 7 bile duct carcinoma, 5 ampulla carcinoma and 4 carcinomas of duodenal papilla. Conclusion: Pancreatic adenocarcinoma is one of the commonly encounted tumors and is still very difficult to diagnose at the early stage and to distinguish from other lesions preoperatively. Our study indicates that PCR SSP is an ideal assay in comparison with other methods to detect K ras gene mutation. It is simple, rapid, specific, sensitive and easily generalized for clinical application on preoperative diagnosis.展开更多
Objective： To detect the style of K-ras gene point mutation in human pancreatic cancer cell line PANC-1 and decide the bp sequence of Ras target position interfered by RNA. Methods： Three kinds of special sequence p...Objective： To detect the style of K-ras gene point mutation in human pancreatic cancer cell line PANC-1 and decide the bp sequence of Ras target position interfered by RNA. Methods： Three kinds of special sequence primers （SSP） for polymerase chain reaction （PCR） with regard to the mutation styles （OAT, COT and GOT） at codon 12 of K-ras were used to study the human pancreatic cancer cell line PANC-1. The amplification products were studied with polyacrylamine gel electrophoresis to detect the style of point mutation. Results： The style of K-ras gene point mutation at codon 12 was OAT in human pancreatic cancer cell line. Conclusion： PCR-SSP is rapid, convenient and high specific. The results provide a basis for further gene therapy by RNA interference for pancreatic cancer.展开更多
Objective: Molecular targeted drugs have been widely used in clinical application which has successfully prolonged some patients' life. Meanwhile, molecular targeted drug therapy for esophageal cancer are attracti...Objective: Molecular targeted drugs have been widely used in clinical application which has successfully prolonged some patients' life. Meanwhile, molecular targeted drug therapy for esophageal cancer are attracting more and more attention from doctors and experts. However, little study has been done towards the effect of this approach for treating esophageal squamous cell carcinoma. This paper, therefore, intends to explore the possibilities of applying EGFR-TKI inhibitors or anti-EGFR monoclonal antibody in esophageal squamous cell carcinoma by studying the mutations of EGFR, K-ras and B-raf in the esophageal squamous cell carcinoma tissues. Methods: Thirty-five cases of resected specimens of diagnosed esophageal squamous cell carcinoma with complete clinical and pathological data from January to April 2009 were collected. Pyrophosphate was used for observing the mutations of EGFR, K-ras and B-raf in the esophageal squamous cell carcinoma tissues. Results: Examinations were undertaken respectively to the codon segment 746-754 of exon 19 in EGFR genes, codon 12 and 13 in K-ras genes as well as condon 600 in B-raf genes. No mutation was found in EGFR and B-raf genes with mutation rate 0% (0/35), all of codon 12 in K-ras genes were wild-type without any mutation, while 2 specimens of codon 13 had mutations with mutation rate of 5.71% (2/35). Conclusion: In treating esophageal squamous cell carcinoma patients, all K-ras genes are expressed as wild type due to low mutation rate; cetuximab is effective due to low mutation rate of B-raf while EGFR-TKI inhibitor will not be effective enough because of low mutation rate of EGFR genes.展开更多
In a total of 83 UN specimens were investigated for proto-oncogene mutations, tumor supressor genes promoter methylation status and c-myc and Ki-67 expression. Point mutations in c-myc were detected in cases with high...In a total of 83 UN specimens were investigated for proto-oncogene mutations, tumor supressor genes promoter methylation status and c-myc and Ki-67 expression. Point mutations in c-myc were detected in cases with high grade and proliferation index. Mutated K-ras proto-onco- gene profiles were detected in 17 (21%) tumoral spiecemens that examined. Tumor specimens were also showed hypermethylated promoter domain for the SFRP2, MGMT tumor supressor genes. These findings showed the combine effect of mutated c-myc and K-ras oncogene and epigenetic inactivation of tissue specific tumor supressor genes (TS) play a crucial role in tumor progression and recurrence in UN carcinogenesis.展开更多
AIMS To examine the prevalance of p53 mutations in hepatocellular carcinoma (HCC) from Chongqing area and the relationship between the p53 mutations and clinicopathological features of HCC,as well as the risk factors....AIMS To examine the prevalance of p53 mutations in hepatocellular carcinoma (HCC) from Chongqing area and the relationship between the p53 mutations and clinicopathological features of HCC,as well as the risk factors. METHODS The overexpression and point mutations of tumor suppressor gene p53 in 38 cases of HCC were detected by a sensitive antigen retrieval fluid (ARF) immunohistochemical method and polymerase chain re- action(PCR)-restriction fragment length polymorphism (RFLP),and single strand conformation polymorphism (SSCP)-silver staining analysis. RESULTS The results showed that 16 of 38 HCCs had positive p53 protein (42.1%),7 HCCs had p53 mutation at 249 (18.4 % ) and 2 HCCS had point muta- tion within exon 7 other than 249. Among 9 cases of HCC with mutations,8 cases demonstrated positive p53 protein,its coincidental rate was 88.9%. The overexpression and mutations of p53 were significantly related to the differentiation and metastasis of HCCs. The frequency of p53 mutations was consistent with high prevalence of HBV and a moderate aflatoxin B1 (AFB1) exposure in our area. CONCLUSIONS The results suggest that AFB1 acts synergistically with HBV in the generation of p53 mutations. Furthermore,dietary exposure to AFB1 may mainly contribute to the tumor specific mutation at codon 249,while HBV may account for other scattered mutations in HCC.展开更多
AIMS p53 gene is one of the focuses in the study of tu- mour suppressor genes.So far,there is still controversy about the relationship between p53 alterations and clinicolpathological parameters of gastic cancers such...AIMS p53 gene is one of the focuses in the study of tu- mour suppressor genes.So far,there is still controversy about the relationship between p53 alterations and clinicolpathological parameters of gastic cancers such as macroscopic classifica- tion,stage,degree of differentiation,depth of tumour invasion and lymphonod metastasis.Tamura has reported that p53 gene mutations mainly occur in the aneuploid tumours.But in China, nothing is reported in this field of study.Our aim is to analyze the relationship between p53 gene mutations and these param- eters including DNA ploidy in Chinese primary gasrtic cancers. METHODS Mutations of the p53 gene in exon5-8 were examined in 20 cases of primary gasric cancer by PCR-SSCP (Polymerase-chain-reaction-single-strand-conforma- tion-polymorphism)analysis. RESULTS Mutations were detected in 8(40%)cases:2 cases in exon5-6,2 cases in exon7,4 cases in exon8.These mutations were detected from stage 0 to stage Ⅲ No significant association was found between p53 gene mutations and the clinicopathological parameters such as macroscopic classifico- tion,degree of histological differentiation,depth of tumour in- vasion and lymphonod metastasis.In addition,66.7%(6 of 9) of aneuploid tumours had p53 mutations and only 18.2%(2 of 11)of diploid tumours had mutations. CONCLUSIONS These results suggest that p53 gene muta- tions are related to DNA ploidy alterations and that p53 gene is one of the important turnout suppressor genes in human gastric cancer.展开更多
AIM To investigate the mechanisms of codon 249 mutation of p53 gene in the formation of hepatocellular carcinoma (HCC). METHODS Codon 249 mutation accompanied by loss of heterozygosity (LOH) and its effect on trans...AIM To investigate the mechanisms of codon 249 mutation of p53 gene in the formation of hepatocellular carcinoma (HCC). METHODS Codon 249 mutation accompanied by loss of heterozygosity (LOH) and its effect on translation and transcription were studied using SSCP, IHC and RT PCR/slot hybridization. RESULTS Codon 249 mutations were detected in 32 9%, LOH detected in 68 4% among the HCC patients. Mutations of condon 249 were accompanied by LOH in 90%. The positive rates of p53 protein and mRNA were 91 3% and 95 7%, in mutational group, both were significantly higher than those in the non mutational group (91 3% vs 19 1% and 95 7% vs 40 4%, respectively, both P <0 01). The translation of p53 gene was strongly related to its transcription by correlation analysis ( r =0 8208). CONCLUSIONS LOH might play an important role in hepatocarcinogenesis of codon 249 mutation, which could increase both transcription and translation of p53 gene. The increased expression of p53 protein mainly depend on the increased transcription of p53 gene.展开更多
AIM To study the significance of p53 gene in hepatocarcinogenesis through analyzing codon 249 mutations of p53 gene in non neoplastic liver tissues. METHODS Codon 249 mutation was detected using single st...AIM To study the significance of p53 gene in hepatocarcinogenesis through analyzing codon 249 mutations of p53 gene in non neoplastic liver tissues. METHODS Codon 249 mutation was detected using single stranded conformational polymorphism analysis and allele specific PCR in liver tissues from 10 cases of chronic hepatitis, 5 cases of cirrhosis and 20 cases of HCCs. RESULTS The detection rate of codon 249 mutation in chronic hepatitis, cirrhosis and pericancerous tissues was 70% (7/10), 100% (5/5) and 70% (14/20), respectively by AS PCR. These mutations could not be detected by SSCP analysis. The detection rates were 65% (13/20) and 45% (9/20) in cancerous tissues by AS PCR and SSCP analysis. CONCLUSION Codon 249 mutations of p53 gene were very popular in non neoplastic liver tissues though the number of those mutant cells was only in subsection. Those mutations in cancerous tissues might take place in the stage before the formation of tumor.展开更多
AIM:To study the characteristics of APC(adenomatous polyposis coli)gene germline mutation in Chinese patients with familial adenomatous polyposis(FAP).METHODS:APC gene from 14 FAP families was amplified by polymerase ...AIM:To study the characteristics of APC(adenomatous polyposis coli)gene germline mutation in Chinese patients with familial adenomatous polyposis(FAP).METHODS:APC gene from 14 FAP families was amplified by polymerase chain reaction(PCR)and underwent direct sequencing to determine the micromutation type.For the samples without micromutation,the large fragment deletion of APC gene was examined by multiplex ligation-dependent probe amplification(MLPA).RESULTS:There were gene micromutations in 9 families with a micromutation detection rate of 64.3%(9/14),including 6 frameshift mutations(66.7%),1 nonsense mutation(11.1%)and 2 splicing mutations(22.2%).Large fragment deletions were detected by MLPA in 2 families.The total mutation detection rate of micromutations and large fragment deletions was 78.6%(11/14).CONCLUSION:The detection rate of APC gene germline mutation can be improved by direct sequencing combined with MLPA large fragment deletion detection.展开更多
Objective To detect the specific mutations in rpoB gene of Mycobacterium tuberculosis by oligonucleotide microarray. Methods Four wild-type and 8 mutant probes were used to detect rifampin resistant strains. Target DN...Objective To detect the specific mutations in rpoB gene of Mycobacterium tuberculosis by oligonucleotide microarray. Methods Four wild-type and 8 mutant probes were used to detect rifampin resistant strains. Target DNA of M. tuberculosis was amplified by PCR, hybridized and scanned. Direct sequencing was performed to verify the results of oligonucleotide microarray Results Of the 102 rifampin-resistant strains 98 （96.1%） had mutations in the rpoB genes. Conclusion Oligonucleotide microarray with mutation-specific probes is a reliable and useful tool for the rapid and accurate diagnosis of rifampin resistance in M. tuberculosis isolates.展开更多
AIM: The pathogenesis of occurrence of liver inflammation and fibrosis in patients with nonalcoholic steatohepatitis (NASH) is not completely understood. Other than insulin resistance, iron abnormalities have been tho...AIM: The pathogenesis of occurrence of liver inflammation and fibrosis in patients with nonalcoholic steatohepatitis (NASH) is not completely understood. Other than insulin resistance, iron abnormalities have been thought to be one of the triggering factors. Therefore, our aim was to study the role of iron abnormalities and HFE gene mutations in patients with NASH. METHODS: Thirty-one patients of NASH diagnosed on the basis of clinical examination biochemistry, ultrasonography and liver biopsy (n = 14) were included in the study. Serum iron parameters (n = 23) (iron, ferritin, total iron-binding capacity and transferrin saturation), Perls' iron staining on liver biopsies (n = 14) and HFE gene mutations (C282Y and H63D) (n = 16) were studied in these patients. The association between iron staining, necroinflammatory activity and fibrosis stage on liver biopsies was also determined. RESULTS: Elevated serum iron, ferritin and transferrin saturation above 55% were observed in 4.3% of patients. On histology, 71% of the patients had negative iron staining, 21.4% had 1+ staining, 7.2% had 2+ staining and none had 3+ or 4+ staining. There was no association between the degree of iron staining and necroinflammatory activity (P=0.55) and fibrosis stage (P= 0.09) on histology. None of the patients had C282Y HFE gene mutation and four patients (25%) were found to be heterozygotes for H63D gene mutation. CONCLUSION: Our study does not favor iron overload and HFE gene mutations as major factors in the pathogenesis of NASH in Asian Indians.展开更多
Von Meyenburg complexes(VMCs) are a rare type of ductal plate malformation. We herein report two Chinese families with VMCs, and the suspicious gene mutation of this disease. Proband A was a 62-year-old woman with abn...Von Meyenburg complexes(VMCs) are a rare type of ductal plate malformation. We herein report two Chinese families with VMCs, and the suspicious gene mutation of this disease. Proband A was a 62-year-old woman with abnormal echographic presentation of the liver. She received magnetic resonance imaging(MRI) examination and liver biopsy, and the results showed she had VMCs. Histologically proved hepatocellular carcinoma was found 1 year after the diagnosis of VMCs. Proband B was a 57-year-old woman with intrahepatic diffuselesions displayed by abdominal ultrasonography. Her final diagnoses were VMCs, congenital hepatic fibrosis, and hepatitis B surface e antigen-negative chronic hepatitis B after a series of examinations. Then, all the family members of both proband A and proband B were screened for VMCs by MRI or ultrasonography. The results showed that four of the 11 family members from two families, including two males and two females, were diagnosed with VMCs. DNA samples were extracted from the peripheral blood of those 11 individuals of two VMCs pedigrees and subjected to polymerase chain reaction amplification of the polycystic kidney and hepatic disease 1(PKHD1) gene. Two different mutation loci were identified. Heterozygous mutations located in exon 32(c.4280 delG, p.Gly1427 ValfsX 6) in family A and exon 28(c.3118 C>T, p.Arg1040 Ter) in family B were detected. We speculate that PKHD1 gene mutations may be responsible for the development of VMCs.展开更多
Birt–Hogg–Dubé(BHD) syndrome, a hereditary renal cancer syndrome caused by mutations in the folliculin(FLCN) gene, is characterized by the presence of ibrofolliculomas, pulmonary cysts, spontaneous pneumothorax...Birt–Hogg–Dubé(BHD) syndrome, a hereditary renal cancer syndrome caused by mutations in the folliculin(FLCN) gene, is characterized by the presence of ibrofolliculomas, pulmonary cysts, spontaneous pneumothorax, and renal cell carcinoma(RCC). Few BHD syndrome cases have been reported in Asian countries, and cutaneous presentations are relatively rare in Asian patients. Asian BHD patients may be misdiagnosed due to their atypical manifestations. Here, we report two Chinese BHD patients with novel FLCN mutations(c.946-947 del AG in exon 9 and c.770-772 del CCT in exon 7). Both of them had RCC and spontaneous pneumothorax without ibrofolliculomas. In patients with RCC and pulmonary cysts but without cutaneous lesions, screening for mutations in the FLCN gene should be performed, especially for those with a family history of RCC or pulmonary cysts(pneumothorax).展开更多
AIM:To describe a Polish population with nonalcoholic fatty liver disease(NAFLD)with regard to HFE gene mutations,as well as analyzing demographic and clinical data.METHODS:Sixty-two consecutive patients with biopsy-p...AIM:To describe a Polish population with nonalcoholic fatty liver disease(NAFLD)with regard to HFE gene mutations,as well as analyzing demographic and clinical data.METHODS:Sixty-two consecutive patients with biopsy-proven NAFLD were included in the study.Demographic,clinical,and laboratory data were summarized in a database.C282Y and H63D mutations of the HFE gene were analyzed using polymerase chain reactionrestriction fragment lenght polymorphism.RESULTS:The analyzed cohort consisted of 62 homo-geneic Caucasian participants,66.1%men and 33.9% women,with a median age of 48 years.The median body mass index was 29.05 kg/m 2 .Hypercholesterolemia was observed in 74.2%of patients and hypertriglyceridemia in 32.2%;16.1%had type 2 diabetes mellitus(DMt2).On liver biopsy,22.6%of NAFLD patients were found to have severe fibrosis.There were no differences between frequencies of HFE gene mutations in subgroups of NAFLD patients with less and more severe liver fibrosis.Obesity,older age,female gender and DMt2 were associated with more advanced fibrosis in this Polish cohort,as well as higher glucose level,serum iron and transaminase aspartate aminotransferase/alanine aminotransferase ratio.CONCLUSION:HFE mutations conferred no additional hepatic fibrosis risk in NAFLD,but higher serum iron was a risk factor for severe liver damage in NAFLD,regardless of HFE mutations.展开更多
基金National Natural Science foundation of China, No.39470332
文摘Objective:To study the role of the mutations of p53, APC and K-ras genes in 47 cases of 3 types of intestinal metaplasia (IM) of gastric mucosa. Methods:In 47 cases of IM, exons 5- 8 of p53 and exons 15 of APC were examined with PCR-SSCP and codon 12 of K-ras with PCR-RFLP to detect the existence of any mutations of these structures. Results:Muta- tions of p53, APC and K-ras were found in 29.8% (14/47),6.4% (3/47) and 6.4% (3/47) respectively in our series of patients who consisted of 33 with types I and II and 14 with type III of IM. The mutation rate of p53 was far higher in patients with type III IM (57.1%,8/14) than in those with types I and II IM(18.2%,6/33)(P <0.05). Though the mutation rate of APC and K-ras was also higher in the patients with type III IM than in those with types I and II IM, it was of no statistical significance (P >0.05). In one case of type III IM, mutation of both p53 and K-ras was found. Conclusion: The molecular changes of 3 types of IM are different. The mutation of p53 may be closely related to carcinogenesis in cases of type III IM and it serve as a sign for the early diagnosis of gastric carcinoma.
基金Supported by Shenzhen High-level Hospital Construction Fund.
文摘BACKGROUND Patients harboring gene mutations like KRAS,NRAS,and BRAF demonstrate highly variable responses to chemotherapy,posing challenges for treatment optimization.Multiparametric magnetic resonance imaging(MRI),with its noninvasive capability to assess tumor characteristics in detail,has shown promise in evaluating treatment response and predicting therapeutic outcomes.This technology holds potential for guiding personalized treatment strategies tailored to individual patient profiles,enhancing the precision and effectiveness of colorectal cancer care.AIM To create a multiparametric MRI-based predictive model for assessing chemotherapy efficacy in colorectal cancer patients with gene mutations.METHODS This retrospective study was conducted in a tertiary hospital,analyzing 157 colorectal cancer patients with gene mutations treated between August 2022 and December 2023.Based on chemotherapy outcomes,the patients were categorized into favorable(n=60)and unfavorable(n=50)response groups.Univariate and multivariate logistic regression analyses were performed to identify independent predictors of chemotherapy efficacy.A predictive nomogram was constructed using significant variables,and its performance was assessed using the area under the receiver operating characteristic curve(AUC)in both training and validation sets.RESULTS Univariate analysis identified that tumor differentiation,T2 signal intensity ratio,tumor-to-anal margin distance,and MRI-detected lymph node metastasis as significantly associated with chemotherapy response(P<0.05).Multivariate Logistics regression confirmed these four parameters as independent predictors.The predictive model demonstrated strong discrimination,with an AUC of 0.938(sensitivity:86%;specificity:92%)in the training set,and 0.942(sensitivity:100%;specificity:83%)in the validation set.CONCLUSION We established and validated a multiparametric MRI-based model for predicting chemotherapy response in colorectal cancer patients with gene mutations.This model holds promise for guiding individualized treatment strategies.
基金supported by the National Natural Science Foundation(82271057)the Natural Science Foundation of Hunan Province(2023JJ30818),China。
文摘Objective:Keratoconus(KC)is a progressive corneal ectasia disorder,arising from a myriad of causes including genetic predispositions,environmental factors,biomechanical influences,and inflammatory reactions.This study aims to identify potential pathogenetic gene mutations in patients with sporadic KC in the Han Chinese population.Methods:Twenty-five patients with primary KC as well as 50 unrelated population matched healthy controls,were included in this study to identify potential pathogenic gene mutations among sporadic KC patients in the Han Chinese population.Sanger sequencing and whole-exome sequencing(WES)were used to analyze mutations in the zinc finger protein 469(ZNF469)gene.Bioinformatics analysis was conducted to explore the potential role of ZNF469 in KC pathogenesis.Results:Five novel heterozygous missense variants were identified in KC patients.Among them,2 compound heterozygous variants,c.8986G>C(p.E2996Q)with c.11765A>C(p.D3922A),and c.4423C>G(p.L1475V)with c.10633G>A(p.G3545R),were determined to be possible pathogenic factors for KC.Conclusion:Mutations in the ZNF469 gene may contribute to the development of KC in the Han Chinese population.These mutation sites may provide valuable information for future genetic screening of KC patients and their families.
基金Supported by The Department of Education of Zhejiang Province of China,grant No.Y200804314the Zhejiang Provincial Natural Science Foundation,grant No.R2090353+1 种基金the Department of Science and Technology of Zhejiang Province,grant No.2008C33039the Chinese Ministry of Health,grant No.N20100148
文摘AIM:To identify and assess mutations in the K-ras and BRAF genes in a cohort of Chinese patients with colorectal cancer (CRC) for their association with various clinicopathological parameters and prognosis.METHODS:Genomic DNA was isolated from frozen tissues.Pyrosequencing analysis was conducted to detect mutations in the K-ras (codons 12,13,and 61) and BRAF genes (codon 600).Statistical analysis was carried out using SPSS-15.0 software.RESULTS:Among the 118 colorectal cancer patients,we detected 41 (34.7%) mutations in the K-ras gene.Mutation frequencies at codon 12 and codon 13 were 23.7% (28/118) and 10.2% (12/118),respectively.Only one patient harbored a point mutation at codon 61 (0.8%,1/118).Gender was the only factor that showed an obvious relationship with K-ras gene mutation (female 44.7% vs male 28.2%,P=0.037).Other clinicopathological features,such as age,location of the tumor,tumor differentiation,Tumor,Node and Metastases classification,and the Union for International Cancer Control staging,showed no positive relationship with K-ras gene mutations.No significant correlation was observed between the presence of K-ras mutations (codons 12,13,and 61) and the survival of the patients.BRAF mutations were rare,and only two patients (1.7%) harbored a detectable mutation at codon 600.CONCLUSION:K-ras gene mutation is a common event in our 118 Chinese CRC patients,with an obvious relationship with gender.However,it seems not to be an independent prognostic factor in CRC patients.The BRAF gene is rarely mutated in Chinese CRC patients.
基金This subject is supported by the Fund for Returned Scientists and Scholars,[1999]363.Chinese Ministry of Education.
文摘AIM:To study the genetic alteration in ACF and to define the possibility that ACF may be a very early morphological lesion with molecular changes,and to explore the relationship between ACF and colorectal adenoma even carcinoma. METHODS: DNA from 35 CRC, 15 adenomas, 34 ACF and 10 normal mucus was isolated by means of microdissection. Direct gene sequencing of K-ras gene including codon 12, 13 and 61 as well as the mutation cluster region (MCR) of APC gene was performed. RESULTS: K-ras gene mutation frequency in ACF, adenoma and carcinoma was 17.6% (6/34), 13.3% (2/15), and 14.3% (5/35) respectively, showing no difference (P 】 0.05) in K-ras gene mutation among three pathologic procedures. The K-ras gene mutation in adenoma, carcinoma and 4 ACF restricted in codon 12 (GGT GAT), but the other 2 mutations from ACF located in codon 13 (GGC GAC). K-ras gene mutation was found more frequently in older patients and patients with polypoid cancer. No mutation in codon 61 was found in the three tissue types. Mutation rate of APC gene in adenoma and carcinoma was 22.9% (8/35) and 26.7% (4/15), which was higher than ACF (2.9%) (P 【0.05). APC gene mutation in carcinoma was not correlated with age of patients, location, size and differentiation of tumor. CONCLUSION: ACF might be a very early morphological lesion in the tumorogenesis of colorectal tumor. The morphological feature and gene mutation status was different in ACF and adenoma. ACF is possibly putative microadenoma that might be the precursor of adenoma. In addition, the development of a subgroup of colorectal carcinomas might undergo a way of normal epithelium ACF carcinomas .
基金Supported by the Key Technologies R&D Program of Hubei Province,No.2002AA301C84.
文摘AIM:To investigate the functions of promoter hypermethylation of O6-methylguanine-DNA methyltransferase(MGMT)gene in colorectal tumorigenesis and progression.METHODS:The promoter hypermethylation of MGMT gene was detected in 27 sporadic colorectal adenomas,62 sporadic colorectal carcinomas and 20 normal colorectal mucosa tissues by methylation-specific PCR.At the same time,the expression of MGMT protein was carried out in the same samples using immunohistochemistry.Mutantallele-specific amplification was used to detect K-rasG to A point mutation in codon 12.RESULTS:None of the normal colorectal mucosa tissues showed methylated bands.Promoter hypermethylation was detected in 40.7%(11 of 27)of adenomas and 43.5%(27 of 62)of carcinomas.MGMT proteins were expressed in nucleus and cytoplasm of normal colorectal mucosa tissues.Loss of MGMT expression was found in 22.2%(6 of 27)of adenomas and 45.2%(28 of 62)of carcinomas.The difference between them was significant(P=0.041).In the 6 adenomas and 28 carcinomas losing MGMT expression,5 and 24 cases presented methylation,respectively(P=0.027,P<0.001).Thirteen of the 19 colorectal tumors with K-rasG to A point mutation in codon 12 had methylated MGMT(P=0.011).The frequencies of K-rasG to A point mutation were 35.3%(12 of 34)and 12.7%(7 of 55)in tumors losing MGMT expression and with normal expression,respectively.CONCLUSION:Promoter hypermethylation and loss of expression of MGMT gene were common events in colorectal tumorigenesis,and loss of expression of MGMT occurs more frequently in carcinomas than in adenomas in sporadic patients.Hypermethylation of the CpG island of MGMT gene was associated with loss of MGMT expression and K-ras G to A point mutation in colorectal tumor.The frequency of K-ras G to A point mutation was increased in tumors losing MGMT expression.It suggests that epigenetic inactivation of MGMT plays an important role in colorectal neoplasia.
文摘To evaluate the feasibility and clinical significance of the PCR SSP technique in detecting K ras gene mutation at codon 12 in pancreatic adenocarcinoma tissues. 80 specimens of surgical resection or biopsy samples were tested at our hospital from January 1994 to September 1995. Three different special sequence primers (SSP) synthesized according to mutation styles of CGT, GTT, GAT were respectively prepared. Three amplification reactions were performed for each sample. The amplification products were analyzed by conventional polyacrylamide gel electrophoresis, stained with ethidium bromide and observed under UV transillumination. Results: All of the 34 pancreatic adenocarcinoma samples had positive PCR results with the mutation rate 100%. 7 cases were CGT mutation, 18 GGT and 17 GAT mutation, in which 2 types of mutation existed in 8 cases. No mutation appeared in 13 normal pancreatic tissues, 6 insulinomas, 6 chronic pancreatitis, 5 benign pancreatic cysts, 7 bile duct carcinoma, 5 ampulla carcinoma and 4 carcinomas of duodenal papilla. Conclusion: Pancreatic adenocarcinoma is one of the commonly encounted tumors and is still very difficult to diagnose at the early stage and to distinguish from other lesions preoperatively. Our study indicates that PCR SSP is an ideal assay in comparison with other methods to detect K ras gene mutation. It is simple, rapid, specific, sensitive and easily generalized for clinical application on preoperative diagnosis.
文摘Objective： To detect the style of K-ras gene point mutation in human pancreatic cancer cell line PANC-1 and decide the bp sequence of Ras target position interfered by RNA. Methods： Three kinds of special sequence primers （SSP） for polymerase chain reaction （PCR） with regard to the mutation styles （OAT, COT and GOT） at codon 12 of K-ras were used to study the human pancreatic cancer cell line PANC-1. The amplification products were studied with polyacrylamine gel electrophoresis to detect the style of point mutation. Results： The style of K-ras gene point mutation at codon 12 was OAT in human pancreatic cancer cell line. Conclusion： PCR-SSP is rapid, convenient and high specific. The results provide a basis for further gene therapy by RNA interference for pancreatic cancer.
文摘Objective: Molecular targeted drugs have been widely used in clinical application which has successfully prolonged some patients' life. Meanwhile, molecular targeted drug therapy for esophageal cancer are attracting more and more attention from doctors and experts. However, little study has been done towards the effect of this approach for treating esophageal squamous cell carcinoma. This paper, therefore, intends to explore the possibilities of applying EGFR-TKI inhibitors or anti-EGFR monoclonal antibody in esophageal squamous cell carcinoma by studying the mutations of EGFR, K-ras and B-raf in the esophageal squamous cell carcinoma tissues. Methods: Thirty-five cases of resected specimens of diagnosed esophageal squamous cell carcinoma with complete clinical and pathological data from January to April 2009 were collected. Pyrophosphate was used for observing the mutations of EGFR, K-ras and B-raf in the esophageal squamous cell carcinoma tissues. Results: Examinations were undertaken respectively to the codon segment 746-754 of exon 19 in EGFR genes, codon 12 and 13 in K-ras genes as well as condon 600 in B-raf genes. No mutation was found in EGFR and B-raf genes with mutation rate 0% (0/35), all of codon 12 in K-ras genes were wild-type without any mutation, while 2 specimens of codon 13 had mutations with mutation rate of 5.71% (2/35). Conclusion: In treating esophageal squamous cell carcinoma patients, all K-ras genes are expressed as wild type due to low mutation rate; cetuximab is effective due to low mutation rate of B-raf while EGFR-TKI inhibitor will not be effective enough because of low mutation rate of EGFR genes.
文摘In a total of 83 UN specimens were investigated for proto-oncogene mutations, tumor supressor genes promoter methylation status and c-myc and Ki-67 expression. Point mutations in c-myc were detected in cases with high grade and proliferation index. Mutated K-ras proto-onco- gene profiles were detected in 17 (21%) tumoral spiecemens that examined. Tumor specimens were also showed hypermethylated promoter domain for the SFRP2, MGMT tumor supressor genes. These findings showed the combine effect of mutated c-myc and K-ras oncogene and epigenetic inactivation of tissue specific tumor supressor genes (TS) play a crucial role in tumor progression and recurrence in UN carcinogenesis.
文摘AIMS To examine the prevalance of p53 mutations in hepatocellular carcinoma (HCC) from Chongqing area and the relationship between the p53 mutations and clinicopathological features of HCC,as well as the risk factors. METHODS The overexpression and point mutations of tumor suppressor gene p53 in 38 cases of HCC were detected by a sensitive antigen retrieval fluid (ARF) immunohistochemical method and polymerase chain re- action(PCR)-restriction fragment length polymorphism (RFLP),and single strand conformation polymorphism (SSCP)-silver staining analysis. RESULTS The results showed that 16 of 38 HCCs had positive p53 protein (42.1%),7 HCCs had p53 mutation at 249 (18.4 % ) and 2 HCCS had point muta- tion within exon 7 other than 249. Among 9 cases of HCC with mutations,8 cases demonstrated positive p53 protein,its coincidental rate was 88.9%. The overexpression and mutations of p53 were significantly related to the differentiation and metastasis of HCCs. The frequency of p53 mutations was consistent with high prevalence of HBV and a moderate aflatoxin B1 (AFB1) exposure in our area. CONCLUSIONS The results suggest that AFB1 acts synergistically with HBV in the generation of p53 mutations. Furthermore,dietary exposure to AFB1 may mainly contribute to the tumor specific mutation at codon 249,while HBV may account for other scattered mutations in HCC.
文摘AIMS p53 gene is one of the focuses in the study of tu- mour suppressor genes.So far,there is still controversy about the relationship between p53 alterations and clinicolpathological parameters of gastic cancers such as macroscopic classifica- tion,stage,degree of differentiation,depth of tumour invasion and lymphonod metastasis.Tamura has reported that p53 gene mutations mainly occur in the aneuploid tumours.But in China, nothing is reported in this field of study.Our aim is to analyze the relationship between p53 gene mutations and these param- eters including DNA ploidy in Chinese primary gasrtic cancers. METHODS Mutations of the p53 gene in exon5-8 were examined in 20 cases of primary gasric cancer by PCR-SSCP (Polymerase-chain-reaction-single-strand-conforma- tion-polymorphism)analysis. RESULTS Mutations were detected in 8(40%)cases:2 cases in exon5-6,2 cases in exon7,4 cases in exon8.These mutations were detected from stage 0 to stage Ⅲ No significant association was found between p53 gene mutations and the clinicopathological parameters such as macroscopic classifico- tion,degree of histological differentiation,depth of tumour in- vasion and lymphonod metastasis.In addition,66.7%(6 of 9) of aneuploid tumours had p53 mutations and only 18.2%(2 of 11)of diploid tumours had mutations. CONCLUSIONS These results suggest that p53 gene muta- tions are related to DNA ploidy alterations and that p53 gene is one of the important turnout suppressor genes in human gastric cancer.
文摘AIM To investigate the mechanisms of codon 249 mutation of p53 gene in the formation of hepatocellular carcinoma (HCC). METHODS Codon 249 mutation accompanied by loss of heterozygosity (LOH) and its effect on translation and transcription were studied using SSCP, IHC and RT PCR/slot hybridization. RESULTS Codon 249 mutations were detected in 32 9%, LOH detected in 68 4% among the HCC patients. Mutations of condon 249 were accompanied by LOH in 90%. The positive rates of p53 protein and mRNA were 91 3% and 95 7%, in mutational group, both were significantly higher than those in the non mutational group (91 3% vs 19 1% and 95 7% vs 40 4%, respectively, both P <0 01). The translation of p53 gene was strongly related to its transcription by correlation analysis ( r =0 8208). CONCLUSIONS LOH might play an important role in hepatocarcinogenesis of codon 249 mutation, which could increase both transcription and translation of p53 gene. The increased expression of p53 protein mainly depend on the increased transcription of p53 gene.
文摘AIM To study the significance of p53 gene in hepatocarcinogenesis through analyzing codon 249 mutations of p53 gene in non neoplastic liver tissues. METHODS Codon 249 mutation was detected using single stranded conformational polymorphism analysis and allele specific PCR in liver tissues from 10 cases of chronic hepatitis, 5 cases of cirrhosis and 20 cases of HCCs. RESULTS The detection rate of codon 249 mutation in chronic hepatitis, cirrhosis and pericancerous tissues was 70% (7/10), 100% (5/5) and 70% (14/20), respectively by AS PCR. These mutations could not be detected by SSCP analysis. The detection rates were 65% (13/20) and 45% (9/20) in cancerous tissues by AS PCR and SSCP analysis. CONCLUSION Codon 249 mutations of p53 gene were very popular in non neoplastic liver tissues though the number of those mutant cells was only in subsection. Those mutations in cancerous tissues might take place in the stage before the formation of tumor.
基金Supported by The National Natural Science Foundation of China,No.30940086
文摘AIM:To study the characteristics of APC(adenomatous polyposis coli)gene germline mutation in Chinese patients with familial adenomatous polyposis(FAP).METHODS:APC gene from 14 FAP families was amplified by polymerase chain reaction(PCR)and underwent direct sequencing to determine the micromutation type.For the samples without micromutation,the large fragment deletion of APC gene was examined by multiplex ligation-dependent probe amplification(MLPA).RESULTS:There were gene micromutations in 9 families with a micromutation detection rate of 64.3%(9/14),including 6 frameshift mutations(66.7%),1 nonsense mutation(11.1%)and 2 splicing mutations(22.2%).Large fragment deletions were detected by MLPA in 2 families.The total mutation detection rate of micromutations and large fragment deletions was 78.6%(11/14).CONCLUSION:The detection rate of APC gene germline mutation can be improved by direct sequencing combined with MLPA large fragment deletion detection.
基金supported by the grant from the National Natural Science Foundation of China (No. 30400018)
文摘Objective To detect the specific mutations in rpoB gene of Mycobacterium tuberculosis by oligonucleotide microarray. Methods Four wild-type and 8 mutant probes were used to detect rifampin resistant strains. Target DNA of M. tuberculosis was amplified by PCR, hybridized and scanned. Direct sequencing was performed to verify the results of oligonucleotide microarray Results Of the 102 rifampin-resistant strains 98 （96.1%） had mutations in the rpoB genes. Conclusion Oligonucleotide microarray with mutation-specific probes is a reliable and useful tool for the rapid and accurate diagnosis of rifampin resistance in M. tuberculosis isolates.
文摘AIM: The pathogenesis of occurrence of liver inflammation and fibrosis in patients with nonalcoholic steatohepatitis (NASH) is not completely understood. Other than insulin resistance, iron abnormalities have been thought to be one of the triggering factors. Therefore, our aim was to study the role of iron abnormalities and HFE gene mutations in patients with NASH. METHODS: Thirty-one patients of NASH diagnosed on the basis of clinical examination biochemistry, ultrasonography and liver biopsy (n = 14) were included in the study. Serum iron parameters (n = 23) (iron, ferritin, total iron-binding capacity and transferrin saturation), Perls' iron staining on liver biopsies (n = 14) and HFE gene mutations (C282Y and H63D) (n = 16) were studied in these patients. The association between iron staining, necroinflammatory activity and fibrosis stage on liver biopsies was also determined. RESULTS: Elevated serum iron, ferritin and transferrin saturation above 55% were observed in 4.3% of patients. On histology, 71% of the patients had negative iron staining, 21.4% had 1+ staining, 7.2% had 2+ staining and none had 3+ or 4+ staining. There was no association between the degree of iron staining and necroinflammatory activity (P=0.55) and fibrosis stage (P= 0.09) on histology. None of the patients had C282Y HFE gene mutation and four patients (25%) were found to be heterozygotes for H63D gene mutation. CONCLUSION: Our study does not favor iron overload and HFE gene mutations as major factors in the pathogenesis of NASH in Asian Indians.
基金Supported by Pilot Project of Fujian Science and Technology Department,No.2015Y0057Fujian Medical Innovation Project,No.2018-ZQN-54Science and Technology Project of Fujian Education Department,No.JAT160211
文摘Von Meyenburg complexes(VMCs) are a rare type of ductal plate malformation. We herein report two Chinese families with VMCs, and the suspicious gene mutation of this disease. Proband A was a 62-year-old woman with abnormal echographic presentation of the liver. She received magnetic resonance imaging(MRI) examination and liver biopsy, and the results showed she had VMCs. Histologically proved hepatocellular carcinoma was found 1 year after the diagnosis of VMCs. Proband B was a 57-year-old woman with intrahepatic diffuselesions displayed by abdominal ultrasonography. Her final diagnoses were VMCs, congenital hepatic fibrosis, and hepatitis B surface e antigen-negative chronic hepatitis B after a series of examinations. Then, all the family members of both proband A and proband B were screened for VMCs by MRI or ultrasonography. The results showed that four of the 11 family members from two families, including two males and two females, were diagnosed with VMCs. DNA samples were extracted from the peripheral blood of those 11 individuals of two VMCs pedigrees and subjected to polymerase chain reaction amplification of the polycystic kidney and hepatic disease 1(PKHD1) gene. Two different mutation loci were identified. Heterozygous mutations located in exon 32(c.4280 delG, p.Gly1427 ValfsX 6) in family A and exon 28(c.3118 C>T, p.Arg1040 Ter) in family B were detected. We speculate that PKHD1 gene mutations may be responsible for the development of VMCs.
基金supported by the National Natural Science Foundation of China(Grant Number:81172418)the Beijing Municipal Natural Science Foundation(Grant Number:7142160)
文摘Birt–Hogg–Dubé(BHD) syndrome, a hereditary renal cancer syndrome caused by mutations in the folliculin(FLCN) gene, is characterized by the presence of ibrofolliculomas, pulmonary cysts, spontaneous pneumothorax, and renal cell carcinoma(RCC). Few BHD syndrome cases have been reported in Asian countries, and cutaneous presentations are relatively rare in Asian patients. Asian BHD patients may be misdiagnosed due to their atypical manifestations. Here, we report two Chinese BHD patients with novel FLCN mutations(c.946-947 del AG in exon 9 and c.770-772 del CCT in exon 7). Both of them had RCC and spontaneous pneumothorax without ibrofolliculomas. In patients with RCC and pulmonary cysts but without cutaneous lesions, screening for mutations in the FLCN gene should be performed, especially for those with a family history of RCC or pulmonary cysts(pneumothorax).
基金Supported by A Grant from a State Committee for Scientific Research,2006-2009,No.N 402 099 21/3037
文摘AIM:To describe a Polish population with nonalcoholic fatty liver disease(NAFLD)with regard to HFE gene mutations,as well as analyzing demographic and clinical data.METHODS:Sixty-two consecutive patients with biopsy-proven NAFLD were included in the study.Demographic,clinical,and laboratory data were summarized in a database.C282Y and H63D mutations of the HFE gene were analyzed using polymerase chain reactionrestriction fragment lenght polymorphism.RESULTS:The analyzed cohort consisted of 62 homo-geneic Caucasian participants,66.1%men and 33.9% women,with a median age of 48 years.The median body mass index was 29.05 kg/m 2 .Hypercholesterolemia was observed in 74.2%of patients and hypertriglyceridemia in 32.2%;16.1%had type 2 diabetes mellitus(DMt2).On liver biopsy,22.6%of NAFLD patients were found to have severe fibrosis.There were no differences between frequencies of HFE gene mutations in subgroups of NAFLD patients with less and more severe liver fibrosis.Obesity,older age,female gender and DMt2 were associated with more advanced fibrosis in this Polish cohort,as well as higher glucose level,serum iron and transaminase aspartate aminotransferase/alanine aminotransferase ratio.CONCLUSION:HFE mutations conferred no additional hepatic fibrosis risk in NAFLD,but higher serum iron was a risk factor for severe liver damage in NAFLD,regardless of HFE mutations.
