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J Med Genet ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381727


BACKGROUND: Early-onset scoliosis (EOS), defined by an onset age of scoliosis less than 10 years, conveys significant health risk to affected children. Identification of the molecular aetiology underlying patients with EOS could provide valuable information for both clinical management and prenatal screening. METHODS: In this study, we consecutively recruited a cohort of 447 Chinese patients with operative EOS. We performed exome sequencing (ES) screening on these individuals and their available family members (totaling 670 subjects). Another cohort of 13 patients with idiopathic early-onset scoliosis (IEOS) from the USA who underwent ES was also recruited. RESULTS: After ES data processing and variant interpretation, we detected molecular diagnostic variants in 92 out of 447 (20.6%) Chinese patients with EOS, including 8 patients with molecular confirmation of their clinical diagnosis and 84 patients with molecular diagnoses of previously unrecognised diseases underlying scoliosis. One out of 13 patients with IEOS from the US cohort was molecularly diagnosed. The age at presentation, the number of organ systems involved and the Cobb angle were the three top features predictive of a molecular diagnosis. CONCLUSION: ES enabled the molecular diagnosis/classification of patients with EOS. Specific clinical features/feature pairs are able to indicate the likelihood of gaining a molecular diagnosis through ES.

BMC Musculoskelet Disord ; 21(1): 220, 2020 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-32278351


BACKGROUND: Klippel-Feil syndrome (KFS) represents a rare anomaly characterized by congenital fusion of the cervical vertebrae. The underlying molecular etiology remains largely unknown because of the genetic and phenotypic heterogeneity. METHODS: We consecutively recruited a Chinese cohort of 37 patients with KFS. The clinical manifestations and radiological assessments were analyzed and whole-exome sequencing (WES) was performed. Additionally, rare variants in KFS cases and controls were compared using genetic burden analysis. RESULTS: We primarily examined rare variants in five reported genes (GDF6, MEOX1, GDF3, MYO18B and RIPPLY2) associated with KFS and detected three variants of uncertain significance in MYO18B. Based on rare variant burden analysis of 96 candidate genes related to vertebral segmentation defects, we identified BAZ1B as having the highest probability of association with KFS, followed by FREM2, SUFU, VANGL1 and KMT2D. In addition, seven patients were proposed to show potential oligogenic inheritance involving more than one variants in candidate genes, the frequency of which was significantly higher than that in the in-house controls. CONCLUSIONS: Our study presents an exome-sequenced cohort and identifies five novel genes potentially associated with KFS, extending the spectrum of known mutations contributing to this syndrome. Furthermore, the genetic burden analysis provides further evidence for potential oligogenic inheritance of KFS.

Expert Rev Gastroenterol Hepatol ; 12(11): 1167-1174, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30152255


BACKGROUND: The purpose of this study is to describe the epidemiological features of bacterial infections caused by multidrug-resistant (MDR) bacteria in cirrhotic patients and their impact on mortality. METHODS: A retrospective study of cirrhotic patients with culture-confirmed bacterial infections was performed between 2011 and 2017. RESULTS: A total of 635 episodes in 563 patients with cirrhosis were included. Bacterial infections caused by MDR isolates accounted for 44.1% (280/635) of the episodes, nearly half of which were hospital acquired (48.4%). The most common MDR isolation site was the respiratory tract (36.4%, 102 episodes), followed by the abdominal cavity (35.4%, 99 episodes). Of the MDR isolates, carbapenem-resistant Enterobacteriaceae (CRE) (91 episodes) were the most common. Patients infected with MDR bacteria had significantly higher mortality than those not infected (25.1% vs 17.4%, p = 0.025). However, this increased mortality could be largely attributed to methicillin-resistant Staphylococcus aureus (MRSA). After adjustment for age, sex, and the model for end-stage liver disease (MELD) score, only MRSA infection was an independent risk factor for 28-day mortality in the multivariable Cox proportional hazard regression model analysis (HR, 2.964, 95% CI (1.175-7.478), p = 0.021). CONCLUSIONS: MDR bacterial infections, especially CRE, have become frequent in patients with cirrhosis in recent years, with MRSA infections significantly increasing short-term mortality.

Antibacterianos/uso terapêutico , Bactérias/patogenicidade , Infecções Bacterianas/epidemiologia , Infecção Hospitalar/epidemiologia , Farmacorresistência Bacteriana Múltipla , Cirrose Hepática/epidemiologia , Adulto , Idoso , Antibacterianos/efeitos adversos , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , China/epidemiologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Infecção Hospitalar/mortalidade , Feminino , Humanos , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
Eur J Gastroenterol Hepatol ; 30(7): 741-746, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29664746


In the past few years, a growing body of clinical evidence has highlighted the risk of vitamin D deficiency in patients with chronic hepatitis C and that vitamin D levels are associated with the course of hepatitis C virus (HCV) infection, adverse effects, and treatment response to peginterferon/ribavirin. Recently, studies have found that vitamin D status is related to drug resistance and increased risk of infection in patients with liver cirrhosis. Vitamin D-related gene polymorphisms have been found to explain the interactions between vitamin D deficiency and HCV infection, offering a new perspective toward understanding the current problems such as the development of insulin resistance and racial differences in sustained virological response. Studies have been conducted to determine whether vitamin D supplementation as an adjuvant yields a better result compared with traditional HCV treatment. Here, we provide a brief review of the past and present knowledge of vitamin D in HCV infection.

Hepacivirus/patogenicidade , Hepatite C Crônica/epidemiologia , Deficiência de Vitamina D/epidemiologia , Antivirais/uso terapêutico , Biomarcadores/sangue , Suplementos Nutricionais , Farmacorresistência Viral , Predisposição Genética para Doença , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Fenótipo , Polimorfismo Genético , Fatores de Risco , Resposta Viral Sustentada , Resultado do Tratamento , Vitamina D/sangue , Vitamina D/uso terapêutico , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/genética
Zhonghua Gan Zang Bing Za Zhi ; 19(1): 55-7, 2011 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-21272461


To investigate the relationship between uncoupling protein 2 (UCP2) expression and the damage caused by oxygen free radicals in acute liver failure rat models. Thirty-five male Sprague-Dawley rats were randomly divided into two groups: the control group (15 rats) and liver failure group (20 rats). The rats were injected intraperitoneally with thioacetamide (TAA) to induce models of acute liver failure. The levels of endotoxin (ET) were detected by double antibody sandwich enzyme-linked immunosorbent assay. The expression of liver UCP2 mRNA was detected by reverse transcription polymerase chain reaction. The superoxide dismutase (SOD) and malonaldehyde (MDA) were detected by spectrophotometry. The expression of UCP2 protein was observed by immunohistochemistry. The data of the two groups were compared using Mann-Whitney U test or ANOVA. The expression of UCP2 mRNA in liver failure group was higher as compared to the control group (P value is less than 0.01); the level of MDA and endotoxin of liver failure group were higher than that of the control group (P value is less than 0.01). SOD of the liver failure group was lower (P value is less than 0.01). There was a certain correlation between UCP2 mRNA expression and ET, SOD and MDA (r = 0.952, -0.667, 0. 634 respectively, P value is less than 0.05 or 0.01). UCP2 is highly expressed in the livers of liver failure rats. A certain correlation perhaps existed between the expression of UCP2 mRNA and the serous SOD, MDA and ET.

Canais Iônicos/metabolismo , Falência Hepática Aguda/metabolismo , Fígado/metabolismo , Proteínas Mitocondriais/metabolismo , Espécies Reativas de Oxigênio/efeitos adversos , Animais , Endotoxinas/análise , Masculino , Malondialdeído/análise , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/análise , Proteína Desacopladora 2