Publications by authors named "Nguyen Van Tung"

10 Publications

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Biliary atresia combined Wilson disease identified by whole exome sequencing in Vietnamese patient with severe liver failure.

Medicine (Baltimore) 2022 Jan;101(2):e28547

Institute of Genome Research, Vietnam Academy of Science and Technology, 18 - Hoang Quoc Viet Str., Caugiay, Hanoi, Vietnam.

Rationale: Hepatobiliary diseases such as biliary atresia (BA), Wilson disease, and progressive familial intrahepatic cholestasis are common causes of morbidity and mortality in young children. Affected patients progress rapidly to end-stage cirrhosis and require liver transplantation or die. Mutations in many genes have been identified to play an important role in the pathogenesis of hepatobiliary diseases.

Patient Concerns And Diagnosis: In this study, we identified mutations in an 8-year-old girl who had severe liver failure. The patient was first diagnosed with BA at 2.5 months of age and has undergone Kasai surgery to connect the umbilical cord and jejunum. After that, the patient suddenly had unusual developments with symptoms of jaundice, acute liver failure with hemolysis. She was tested and diagnosed with Wilson disease.

Interventions And Outcomes: She was treated according to the regimen for a patient with Wilson disease but had abnormal progress leading to severe liver failure. Genetic analysis was performed by whole exome sequencing and Sanger sequencing methods. The genetic analysis revealed that the patient had a homozygous mutation (p.Gly17Glyfs77∗) in the KRT18 gene, a double heterozygous mutation (p.Ser105∗ and p.Pro992Leu) in the ATP7B gene, and a homozygous variant (p.Val444Ala) in the ABCB11 gene. In silico prediction of mutations indicated that these mutations are the cause of the severe liver failure in the patient.

Lesson: This is a rare clinical case of a BA patient combined with Wilson disease. Our results suggested that whole exome sequencing is an effective diagnostic tool and emphasizes the importance of early diagnosis and appropriate management to save lives and prevent serious complications in the patient.
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http://dx.doi.org/10.1097/MD.0000000000028547DOI Listing
January 2022

The role of p.Val444Ala variant in the ABCB11 gene and susceptibility to biliary atresia in Vietnamese patients.

Medicine (Baltimore) 2021 Nov;100(47):e28011

Institute of Genome Research, Vietnam Academy of Science and Technology, Vietnam.

Abstract: Biliary atresia (BA) is the most serious type of obstructive cholangiopathy that occurs in infants. BA can be the cause of death in children under 2 years if untreated early. However, the etiology of the disease is not known. BA is considered to be the result of the destruction of the bile duct system including the accumulation of bile acids. The bile salt export pump, a transporter protein encoded by the ABCB11 gene, plays the main role in the exportation and accumulation of bile acids. The p.Val444Ala variant in this gene is known to be associated with many cholestatic diseases. However, to date no study have been performed to evaluate the association of this variant with susceptibility to the risk of BA. In this study, we aimed to identify the frequency of p.Val444Ala variant and the risk of BA in Vietnamese patients.The polymerase chain reaction (PCR)- restriction fragment length polymorphism method was used to determine the frequency of alleles c.1331T>C (p.Val444Ala, rs2287622) in the ABCB11 gene in 266 Vietnamese patients with BA and 150 healthy people. The gene segment containing the variant was amplified by PCR with specific primers, after that the PCR products were cut by HaeIII restriction enzyme and analyzed on agarose gel to determine the genotypes. The frequency of alleles was assessed statistically to determine the association between these alleles and the risk of disease in patients.In our study, the frequency of alleles c.1331T>C (p.Val444Ala, rs2287622) in the ABCB11 gene was investigated the first time in the patients with BA. The results showed that CC and TC genotypes were significantly different between BA patients and healthy people (P < .01), and the C allele was associated with an increased risk of BA (odds ratio = 2.47; 95% confidence interval: 1.84-3.32; P < .01). The initial results of clinical, biochemical, and genetic analysis in our study suggested that the p.Val444Ala variant in the ABCB11 gene may be a susceptibility factor for the disease in Vietnamese patients with BA. These results provided new insights into the role of this ABCB11 variant in the pathogenesis of BA.
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http://dx.doi.org/10.1097/MD.0000000000028011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615439PMC
November 2021

Two novel CD40LG gene mutations causing X-linked hyper IgM syndrome in Vietnamese patients.

Clin Exp Med 2021 Nov 29. Epub 2021 Nov 29.

Institute of Genome Research, Vietnam Academy of Science and Technology, 18 - Hoang Quoc Viet str., Caugiay, Hanoi, Vietnam.

The X-linked hyper IgM syndrome is a primary immunodeficiency disorder (PID) due to mutations in the CD40LG gene. Hyper IgM syndrome is characterized by the absence or decreased levels of IgG and IgA and normal or elevated IgM levels in serum. Affected patients become susceptible to infections such as pneumonia, diarrhea, and skin ulcer types. Hematopoietic stem cell transplantation is the only treatment currently available and ideally performed before the age of 10 years. Early, accurate diagnosis will contribute to the effective treatment for patients with hyper IgM. The patients from different Vietnamese families who have been diagnosed with hyper IgM at The Allergy, Immunology and Rheumatology Department, Vietnam National Hospital Pediatrics, were performed a genetic analysis using whole exome sequencing. The mutations were confirmed by the Sanger sequencing method in patients and their families. The influence of the mutations was predicted with the in silico analysis tools: PROVEAN, SIFT, PolyPhen-2, and MutationTaster. In this study, two novel mutations (p.Thr254fs and p.Leu138Phe) in the CD40LG gene were found in Vietnamese patients with X-linked hyper IgM syndrome. Our results contribute to the general understanding of the etiology of the disease and can help diagnose the different forms of PID.
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http://dx.doi.org/10.1007/s10238-021-00774-0DOI Listing
November 2021

Anti-inflammatory norclerodane diterpenoids and tetrahydrophenanthrene from the leaves and stems of Dioscorea bulbifera.

Fitoterapia 2021 Sep 12;153:104965. Epub 2021 Jun 12.

Institute of Marine Biochemistry, Vietnam Academy of Science and Technology (VAST), Hanoi 10072, Viet Nam. Electronic address:

Chemical investigation of the leaves and stems of Dioscorea bulbifera resulted in isolation of 10 compounds, including three new norclerodane diterpenoids, diosbulbiferins A (1) and B (2) and diosbulbiferinoside A (3), and one new natural congener, diosbulbiferin C (4), along with one new tetrahydrophenanthrene, diosbulbinone (8). Their structures were elucidated by comprehensive analyses of spectroscopic methods, including NMR and mass spectra. The absolute configurations of compounds 1-3 and 8 were deduced by time-dependent density functional theory (TD-DFT) electronic circular dichroism (ECD) spectroscopic analyses. In addition, cytotoxic effects against MCF-7, HepG2, and SK-Mel-2 cancer cells and in vitro anti-inflammatory effects of the isolated compounds in LPS-stimulated BV2 microglial cells were also reported.
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http://dx.doi.org/10.1016/j.fitote.2021.104965DOI Listing
September 2021

Characterization of a thermophilic cytochrome P450 of the CYP203A subfamily from Binh Chau hot spring in Vietnam.

FEBS Open Bio 2021 01 30;11(1):124-132. Epub 2020 Nov 30.

Department of Biochemistry, Saarland University, Saarbrucken, Germany.

Cytochromes P450 (CYPs or P450s) comprise a superfamily of heme-containing monooxygenases that are involved in a variety of biological processes. CYPs have broad utilities in industry, but most exhibit low thermostability, limiting their use on an industrial scale. Highly thermostable enzymes can be obtained from thermophiles in geothermal areas, including hot springs, offshore oil-producing wells and volcanoes. Here, we report the identification of a gene encoding for a thermophilic CYP from the Binh Chau hot spring metagenomic database, which was designated as P450-T2. The deduced amino acid sequence showed the highest identity of 73.15% with CYP203A1 of Rhodopseudomonas palustris, supporting that P450-T2 is a member of the CYP203A subfamily. Recombinant protein expression yielded 541 nm. The optimal temperature and pH of P450-T2 were 50 °C and 8.0, respectively. The half-life of P450-T2 was 50.2 min at 50 °C, and its melting temperature was 56.80 ± 0.08 °C. It was found to accept electrons from all tested redox partners systems, with BmCPR-Fdx2 being the most effective partner. Screening for putative substrates revealed binding of phenolic compounds, such as l-mimosine and emodin, suggesting a potential application of this new thermophilic P450 in the production of the corresponding hydroxylated products.
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http://dx.doi.org/10.1002/2211-5463.13033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780096PMC
January 2021

A novel frameshift PHKA2 mutation in a family with glycogen storage disease type IXa: A first report in Vietnam and review of literature.

Clin Chim Acta 2020 Sep 7;508:9-15. Epub 2020 May 7.

Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet str., Cau Giay, Hanoi 100000, Viet Nam; Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet str., Cau Giay, Hanoi 100000, Viet Nam. Electronic address:

Background: Glycogen storage diseases (GSDs) are clinically and genetically heterogeneous disorders. Overlapping features between liver GSDs are a major challenge in the clinical diagnosis of them. Genetic testing can provide an early and accurate diagnosis of patients suspected with GSDs.

Case Presentation: In this study, we report two siblings born to healthy, non-consanguineous Vietnamese parents with hepatomegaly. The proband presented with hepatomegaly, normal spleen, elevated transaminases, without hypoglycemia, normal lactate dehydrogenase and creatine kinase. Liver biopsy revealed degeneration and swollen hepatocytes, suggesting a diagnosis with GSDs.

Methods: Whole exome sequencing was applied to identify genetic variants in the proband. Variant validation and familial co-segregation analysis were examined using Sanger sequencing.

Results: A novel frameshift duplication mutation c.3308_3312dupATGTC (p.L1105Mfs*11) of the PHKA2 gene was identified in the proband and his elder brother at the hemizygous state. This mutation was inherited from their mother. Their father and younger brother were normal genotype.

Conclusions: The two siblings were accurately diagnosed with GSD type XIa. This is the first case report of GSD type IXa in Vietnamese patients with a mutation in the PHKA2 gene. This finding may support for genetics diagnosis of unknown cause of hepatomegaly.
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http://dx.doi.org/10.1016/j.cca.2020.05.010DOI Listing
September 2020

De novo Mutations in Vietnamese Patients with Cornelia de Lange Syndrome.

Medicina (Kaunas) 2020 Feb 14;56(2). Epub 2020 Feb 14.

Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet str., Cau Giay, Hanoi 100000, Vietnam.

Cornelia de Lange Syndrome (CdLS) is a rare congenital genetic disease causing abnormal unique facial phenotypes, several defects in organs and body parts, and mental disorder or intellectual disorder traits. Main causes of CdLS have been reported as variants in cohesin complex genes, in which mutations in the gene have been estimated to account for up to 80%. Our study included three Vietnamese patients with typical CdLS phenotypes. Whole exome sequencing revealed two known heterozygous mutations c.6697G>A (p.Val2233Met) and c.2602C>T (p.Arg868X), and a novel heterozygous mutation c.4504delG (p.Val1502fsX87) in the gene of the three patients. In silico analyses of the identified mutations predicted possible damaging and truncating effects on the NIPBL protein. Inherited analyses in the patients' families showed that all of the mutations are de novo. Our results lead a definitive diagnosis of patients with CdLS and expand the spectrum of mutations in the gene. These findings also confirm whole exome sequencing is an efficient tool for genetic screening of CdLS.
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http://dx.doi.org/10.3390/medicina56020076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073647PMC
February 2020

Epidemiological Characteristics of Advanced Hepatocellular Carcinoma in the Northern Region of Vietnam.

Cancer Control 2019 Jan-Dec;26(1):1073274819862793

1 Department of Oncology, Hanoi Medical University, Ton That Tung, Hanoi, Vietnam.

Epidemiological characteristics of hepatocellular carcinoma (HCC) in Southern Vietnam has been well reported as in Globocan 2018 while data from the North has still not been fully presented. Therefore, we conducted this retrospective descriptive study on 198 advanced HCC patients treated at 3 major hospitals in Northern Vietnam to describe demographic features, HCC risk factors, and correlation among them in patients with advanced HCC. This information will lead to prevention efforts and provide information for allocating funds for treatment. The median age at diagnosis was 57 years (range: 19-86) and the male/female ratio was 8.9/1. The proportions of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were 81.3% and 5.6%, respectively. Hepatitis C virus infection rate was significantly higher in patients <50 years old (12.5% vs 3.3%, = .016). There was no significant difference in age or viral hepatitis infection status by gender. Only 7.6% of patients diagnosed with advanced HCC were asymptomatic. In conclusion, with the high rate of HBV infection among patients with advanced HCC, it is necessary for increasing prevention efforts in HBV screening. Furthermore, HCV infection should be noticed in patients with advanced HCC younger than 50 years old.
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http://dx.doi.org/10.1177/1073274819862793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620729PMC
December 2019

The Role of p.Ser1105Ser (in Gene) and p.Arg548Leu (in Gene) with Disease Status of Vietnamese Patients with Congenital Nephrotic Syndrome: Benign or Pathogenic?

Medicina (Kaunas) 2019 Apr 12;55(4). Epub 2019 Apr 12.

L'Hôpital Français de Hanoi, Ministry of Health, 1, Phuong Mai str., Dongda, Hanoi 100000, Vietnam.

: Congenital nephrotic syndrome (CNS), a genetic disease caused by mutations in genes on autosomes, usually occurs in the first three months after birth. A number of genetic mutations in genes, which encode for the components of the glomerular filtration barrier have been identified. We investigated mutations in , , , and genes that relate to the disease in Vietnamese patients. : We performed genetic analysis of two unrelated patients, who were diagnosed with CNS in the Vietnam National Children's Hospital with different disease status. The entire coding region and adjacent splice sites of these genes were amplified and sequenced using the Sanger method. The sequencing data were analyzed and compared with the and gene sequences published in Ensembl (ENSG00000161270, ENSG00000116218, ENSG00000138193, and ENSG00000184937, respectively) using BioEdit software to detect mutations. : We detected a new variant p.Ser607Arg and two other (p.Glu117Lys and p.Ser1105Ser) in the gene, as well as two variants (p.Arg548Leu, p.Pro1575Arg) in the gene. No mutations were detected in the and genes. Patient 1, who presented a heterozygous genotype of p.Ser1105Ser and p.Arg548Leu had a mild disease status but patient 2, who presented a homozygous genotype of these alleles, had a severe phenotype. : These results suggest that variants p.Ser1105Ser (in gene) and p.Arg548Leu (in gene) in the homozygous form might play a role in the development of the disease in patients.
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http://dx.doi.org/10.3390/medicina55040102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524047PMC
April 2019

Transcriptome Sequencing and Analysis of Changes Associated with Insecticide Resistance in the Dengue Mosquito () in Vietnam.

Am J Trop Med Hyg 2019 05;100(5):1240-1248

National Institute of Malariology Parasitology and Entomology, Hanoi, Vietnam.

The mosquito is a transmission vector for dangerous epidemic diseases in humans. Insecticides have been used as the most general vector control method in the world. However, have developed many resistant mechanisms such as reduced neuronal sensitivity to insecticides (target-site resistance), enhanced insecticide metabolism (metabolic resistance), altered transport, sequestration, and other mechanisms. It has become a major problem for vector control programs. Transcriptome sequencing and bioinformatic analysis were used to compare transcription levels between a susceptible strain (Bora7) and a resistant strain (KhanhHoa7) collected from the field. A total of 161 million Illumina reads, including 66,076,678 reads from the Bora7 strain and 69,606,654 reads from the KhanhHoa7 strain, were generated and assembled into 11,174 genes. A comparison of the KhanhHoa7 transcriptome to that of Bora7 showed 672 upregulated genes and 488 downregulated genes. We identified the highly upregulated genes: cytochrome P450 , , , , isoform X2, , isoform X2, , , , , and ; Glutathione S transferase (GST1), UGT1-3, 1-7, 2B15, and 2B37; binding cassette transporter (ABC) transporter F family member 4 and ABC transporter G family member 20. Interestingly, there was a significant increase in the expression of the genes such as (8.3-fold), (5.9-fold), (5.4-fold), (5.4-fold), (5.2-fold), (3.5-fold), and ABC transporter 4 (2.1-fold). Our results suggested a potential relationship between the expression of the genes in metabolic processes and insecticide resistance in the studied strain. These results may contribute to the understanding of the mechanisms of insecticide resistance in .
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http://dx.doi.org/10.4269/ajtmh.18-0607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493926PMC
May 2019
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