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BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare disorder characterized by multiple gastrointestinal hamartomatous polyps and mucocutaneous pigmentation. STK11 has been identified as a causative gene for this disease. CASE PRESENTATION: Herein we report a Chinese Han kindred with PJS. Onset for the PJS signs in three of the patients was rarely as early as at birth. We identified a novel heterozygous mutation (c.440_441delGT, p.Arg147Leufs*15) in the gene STK11, causing a short frameshift followed by a deletion of 63% of the amino acids in the STK protein. This mutation co-segregated with the PJS phenotype, and was absent in two hundred of unrelated ethnicity-matched controls. The mutation led to expression decrease of unaffected STK11 protein in patients than in controls, as well in PJ polyps than in circulating leucocytes from the patients. Phosphorylation levels of the downstream kinase AMPKα altered according with the expression of STK11. These results indicated the possibility that haploinsufficiency and epigenetic reduction of STK11 contributed to the pathogenesis of the disease. CONCLUSION: This study identifies a novel mutation in the pathogenic gene STK11 leading to PJS.
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Mutación de Línea Germinal , Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinasas/genética , Quinasas de la Proteína-Quinasa Activada por el AMP , Adolescente , Secuencia de Bases , ADN/química , ADN/aislamiento & purificación , ADN/metabolismo , Exones , Mutación del Sistema de Lectura , Heterocigoto , Humanos , Masculino , Linaje , Síndrome de Peutz-Jeghers/diagnóstico , Síndrome de Peutz-Jeghers/patología , Análisis de Secuencia de ADNRESUMEN
A large-scale meta-analysis of 14 genome-wide association studies has identified and replicated a series of susceptibility polymorphisms for coronary artery disease (CAD) in European ancestry populations, but evidences for the associations of these loci with CAD in other ethnicities remain lacking. Herein we investigated the associations between ten (rs579459, rs12413409, rs964184, rs4773144, rs2895811, rs3825807, rs216172, rs12936587, rs46522 and rs3798220) of these loci and CAD in Southern Han Chinese (CHS). Genotyping was performed in 1716 CAD patients and 1572 controls using mass spectrography. Both allelic and genotypic associations of rs964184, rs2895811 and rs3798220 with CAD were significant, regardless of adjustment for covariates of gender, age, hypertension, type 2 diabetes, blood lipid profiles and smoking. Significant association of rs12413409 was initially not observed, but after the adjustment for the covariates, both allelic and genotypic associations were identified as significant. Neither allelic nor genotypic association of the other six polymorphisms with CAD was significant regardless of the adjustment. Our results indicated that four loci of the total 10 were associated with CAD in CHS. Therefore, some of the CAD-related loci in European ancestry populations are indeed susceptibility loci for the risk of CAD in Han Chinese.
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Pueblo Asiatico/genética , Enfermedad de la Arteria Coronaria/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Alelos , Estudios de Casos y Controles , China , Enfermedad de la Arteria Coronaria/diagnóstico , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Oportunidad Relativa , RiesgoRESUMEN
The first genome-wide association study for coronary artery disease (CAD) in the Han Chinese population, we reported recently, had identified rs6903956 in gene ADTRP on chromosome 6p24.1 as a novel susceptibility locus for CAD. The risk allele of rs6903956 was associated with decreased mRNA expression of ADTRP. To further study the correlation of ADTRP expression and CAD, in this study we evaluated the associations of eight common variants in the expression-regulating regions of ADTRP with CAD in the Southern Han Chinese population. Rs169790 in 3'UTR, rs2076189 in 5'UTR, four SNPs (rs2076188, rs7753407, rs11966356 and rs1018383) in promoter, and two SNPs (rs3734273, rs80355771) in the last intron of ADTRP were genotyped in 1716 CAD patients and 1572 controls. The correlations between these loci and total or early-onset CAD were investigated. None of these loci was discovered to associate with total CAD (P > 0.05). However, with early-onset CAD, significant both allelic and genotypic associations of rs7753407, rs11966356 and rs1018383 were identified, after adjustment for risk factors of age, gender, hypertension, diabetes, lipid profiles and smoking (adjusted P < 0.05). A haplotype AGCG (constructed by rs2076188, rs7753407, rs11966356 and rs1018383) was identified to protect subjects from early-onset CAD (OR = 0.332, 95% CI = 0.105-0.879, adjusted P = 0.010). Real-time quantitative reverse transcription polymerase chain reaction assay showed that the risk alleles of the associated loci were significantly associated with decreased expression of ADTRP mRNA. Moreover, the average level of ADTRP mRNA expression in early-onset CAD cases was significantly lower than that in controls. Our results provide new evidence supporting the association of ADTRP with the pathogenesis of early-onset CAD.
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Pueblo Asiatico/etnología , Enfermedad de la Arteria Coronaria/genética , Etnicidad/genética , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas/genética , Regiones no Traducidas 3'/genética , Regiones no Traducidas 5'/genética , Anciano , Pueblo Asiatico/genética , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad/genética , Técnicas de Genotipaje , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To explore the forensic pathological features of death caused by anaphylactic shock. METHODS: One hundred and forty-two death cases of anaphylactic shock were retrospectively analyzed. The IgE level in the serum of anaphylactic shock cases were statistically compared with that of 62 non-anaphylactic shock cases. RESULTS: Most cases (77.46%) of anaphylactic shock death occurred in the medical institutes, with intravenous drug administration accounting for 53.53% of anaphylactic shock death. ß-Lactam antibiotics, glucocorticoid and herbal medications were responsible for a significant proportion of such cases. Although characteristic histopathological changes were absent in vast majority of these anaphylactic shock cases, the differences of IgE levels in the serum between anaphylactic shock group and non-anaphylactic shock group were statistically significant (P<0.05). CONCLUSION: Combined information including clinical data, autopsy results, IgE level, and other specific test results should be evaluated together in the forensic pathological diagnosis of anaphylactic shock.
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Anafilaxia , Causas de Muerte , Patologia Forense , Autopsia , Humanos , Infusiones Intravenosas , Estudios Retrospectivos , SueroRESUMEN
Pien Tze Huang (PZH) is a well-known Chinese medicine that has been used as a therapeutic drug in the treatment of a number of diseases, such as hepatocellular carcinoma and colon cancer. However, few studies have analyzed the effects of PZH on ovarian cancer cell proliferation. In the present study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays, cell cycle and apoptosis rate analyses and western blotting were conducted to investigate the effects of PZH on the proliferation rate of ovarian cancer cells and its potential molecular pathway. The results showed that PZH inhibits the proliferation of the human ovarian cancer OVCAR-3 cell line by blocking the progression of the cell cycle from the G1 to S phase, however, PZH did not induce OVCAR-3 cell apoptosis. Increased PZH concentration may downregulate the expression of AKT, phosphorylated (p)-AKT, mammalian target of rapamycin (mTOR) and p-mTOR proteins in the OVCAR-3 cell line. In addition, it was observed that PZH may suppress the protein expression of cyclin-dependent kinase (CDK)4 and CDK6. Overall, the results of the present study indicated that PZH may inhibit ovarian cancer cell proliferation by modulating the activity of the AKT-mTOR pathway.
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OBJECTIVE: To explore the cause of death, clinical manifestations and forensic pathological features of death cases caused by aortic dissection. METHODS: Sixty-three cases of aortic dissection were selected from forensic medical center, Sun Yat-sen University from 2001 to 2011 and retrospectively analyzed. RESULTS: The patients were mostly young and middle-aged male, aged from 30 to 49 years old. The DeBakey type II was the most common pathological type and the main cause of death was pericardial tamponade. The most common symptom was abdominal pain. However, the location of aorta dissection did not always correlate with the location of pain. Some cases showed no obvious clinical symptoms. The rupture was usually located in ascending aorta with atherosclerosis and pathological changes of hypertension. CONCLUSION: It is significant for diagnosis and evaluation the cause of death of aortic dissection by knowing the clinical symptoms and forensic pathological features.
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Aorta/patología , Aneurisma de la Aorta/diagnóstico , Disección Aórtica/diagnóstico , Muerte Súbita/etiología , Adulto , Factores de Edad , Anciano , Disección Aórtica/complicaciones , Disección Aórtica/patología , Aneurisma de la Aorta/complicaciones , Aneurisma de la Aorta/patología , Rotura de la Aorta/complicaciones , Rotura de la Aorta/diagnóstico , Rotura de la Aorta/patología , Taponamiento Cardíaco/complicaciones , Taponamiento Cardíaco/patología , Muerte Súbita/patología , Errores Diagnósticos , Femenino , Patologia Forense , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
OBJECTIVE: To investigate KCNQ1, KCNH2, KCNE1 and KCNE2 gene variants in the cases of sudden manhood death syndrome (SMDS). METHODS: One hundred and sixteen sporadic cases of SMDS and one hundred and twenty-five healthy controlled samples were enrolled. Genomic DNA was extracted from blood samples. Gene variants of KCNQ1, KCNH2, KCNE1 and KCNE2 were screened by direct sequencing. RESULTS: A total of 14 mutations and 14 SNP were detected. Two non-synonymous mutations of them were newfound. There was no non-synonymous mutation found in the control group. CONCLUSION: There are KCNQ1, KCNH2, KCNE1 and KCNE2 gene variants found in Chinese SMDS cases. KCNQ1, KCNH2, KCNE1 and KCNE2 gene mutation may correlate partly with the occurrence of some cases of the SMDS in China.
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Muerte Súbita/etnología , Canales de Potasio Éter-A-Go-Go/genética , Canal de Potasio KCNQ1/genética , Canales de Potasio con Entrada de Voltaje/genética , Secuencia de Bases , Estudios de Casos y Controles , China , Análisis Mutacional de ADN , Canal de Potasio ERG1 , Humanos , Síndrome de QT Prolongado , Mutación , Polimorfismo de Nucleótido Simple , Canales de PotasioRESUMEN
OBJECTIVE: To establish more sensitive methods for detection of DYS385 in routine forensic casework. METHODS: The primers recommended by Genome Database (GDB) and Schneider were used to amplify DYS385 respectively. Then, a semi-nested PCR of DYS385 was designed by using the two different primers as outer and inner primer. A series of experiments were carried out to achieve good result by adjusting the ratio of outer/inner primer and optimizing the PCR condition. RESULTS: It showed that an overall 112 bp shorter DYS385 fragments and better electrophoretic separation were obtained by using primer2B. By using the semi-nested PCR approach, the shorter specific DYS385 fragments could be amplified and detectable DNA amounted to 50 pg. CONCLUSION: This method is 20 fold more sensitive than the ordinary method.