Publications by authors named "Nguyen Thi Kim Lien"

13 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

Effect of Magnetic Magnetite (Fe₃O₄) Nanoparticle Size on Arsenic (V) Removal from Water.

J Nanosci Nanotechnol 2021 04;21(4):2576-2581

Advanced Institute for Science and Technology, Hanoi University of Science and Technology, Hanoi 112400, Vietnam.

Magnetic magnetite (Fe₃O₄) nanoparticles with average sizes of 5.11, 10.53, and 14.76 nm were synthesized by the chemical co-precipitation method. The surface area of Fe₃O₄ nanoparticles (average size of 5.11 nm) had the largest value of 167 m²/g. The adsorption capacity for removing arsenic (As(V)) from water at 3 ppm concentration was investigated by atomic absorption spectroscopy. Results showed that the As(V) adsorption capacity of Fe₃O₄ was dependent on particle size. The maximum absorption efficiency () reached 99.02%, the equilibrium time was 30 min; the maximum Langmuir isotherm adsorption capacity was 14.46 mg/g with Fe₃O₄ nanoparticle an average size of 5 nm. The results indicate that reducing the size of Fe₃O₄ nanoparticles is a promised way for As(V) ion removal from water and wastewater treatment.
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http://dx.doi.org/10.1166/jnn.2021.19113DOI Listing
April 2021

Investigation of the gut microbiome of Apis cerana honeybees from Vietnam.

Biotechnol Lett 2020 Nov 23;42(11):2309-2317. Epub 2020 Jun 23.

Molecular Microbiology Lab, Institute of Biotechnology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.

Objectives: In this study, the gut microbiome of healthy adult honeybees, Apis cerana, was investigated by sequencing the V3 - V4 region in 16S rRNA gene using Illumina Miseq platform.

Results: The total of 37,853 reads for 16S rRNA gene were obtained and 30,121 (79.6%) reads were valid with 25,291 (84.0%) reads that were classified into 116 species belonging to four major phyla. The relative abundances of the bacterial isolates in honeybee samples were phylum Proteobacteria (70.7%), Actinobacteria (10.7%), Firmicutes (10.3%), and Bacteroidetes (8.4%), respectively. Lactic acid bacteria comprised 18.95% with 10 groups including Bifidobacterium asteroides, B. indicum, Fructobacillus fructosus, Lactobacillus apinorum, L. apis, L. helsingborgensis, L. kimbladii, L. kullabergensis, and L. kunkeei.

Conclusions: The presence of beneficial bacteria in the gut highlighted their role in the honeybee and suggested that they can be promising candidates for the development of probiotics for health improvement, infection control and disease management of honeybees.
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http://dx.doi.org/10.1007/s10529-020-02948-4DOI Listing
November 2020

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

A Novel Nonsense Mutation c.374C>G in CYP21A2 Gene of a Vietnamese Patient with Congenital Adrenal Hyperplasia.

Adv Exp Med Biol 2020 ;1292:27-35

Center for Gene and Protein Research, Hanoi Medical University, Hanoi, Vietnam.

Inactivating mutations of the CYP21A2 gene, encoding for steroid synthesis, have been reported in patients with congenital adrenal hyperplasia (CAH). We report a case of an infant who were diagnosed with CAH and presented with the severe phenotype of CAH with symptoms such as increased testicular volume, elevated of 17-hydroxyprogesteron, testosterone and progesterone. In this study, we established an assay for the detection of unusual genetic in the CYP21A2 gene in the proband and his family. A novel nonsense mutation c.374C > G which caused a substitutions of Serine for a stop codon at codon 125 (p.S125) within exon 3 was found in the proband. Parental genotype studies confirmed carrier state in the father, but the mother showed a wild allele by PCR and sequencing. This inspired us to find deletions using multiplex ligation-dependent probe amplification (MLPA) technique. The probands were found to have a large deletion in exons 1 and 3, while the mother only had deletion in exon 1. Therefore, mutation c.374C > G (p.S125) in the proband is considered as a heterozygous deletion. This mutation caused a truncated protein which lead to the salt wasting CAH phenotype of the proband. This novel nonsense mutation expands the CYP21A2 mutation spectrum in CAH disorder. This case also highlights the need of caution when interpreting results of molecular genetic testing during genetic counseling.
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http://dx.doi.org/10.1007/5584_2018_300DOI Listing
January 2021

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

Three novel mutations in the ATP7B gene of unrelated Vietnamese patients with Wilson disease.

BMC Med Genet 2018 06 18;19(1):104. Epub 2018 Jun 18.

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

Background: Wilson disease (OMIM # 277900) is a autosomal recessive disorder characterized by accumulation of copper in liver and brain. The accumulation of copper resulting in oxidative stress and eventually cell death. The disease has an onset in a childhood and result in a significant neurological impairment or require lifelong treatment. Another serious consequence of the disease is the development of liver damage and acute liver failure leading to liver transplant. The disorder is caused by mutations in the ATP7B gene, encoding a P-type copper transporting ATPase.

Case Presentation: We performed genetic analysis of three unrelated patients from three different Vietnamese families. These patients had clinical features such as numbness of hands and feet, vomiting, insomnia, palsy, liver failure and Kayser-Fleischer (K-F) rings and were diagnosed with Wilson disease in the Human Genetics Department, Vietnam National Children's Hospital. The entire coding region and adjacent splice sites of ATP7B gene were amplified and sequenced by Sanger method. Sequencing data were analyzed and compared with the ATP7B gene sequence published in Ensembl (ENSG00000123191) by using BioEdit software to detect mutations.

Conclusions: In this study, five mutations in the ATP7B gene were found. Among of these, three mutations were novel: c.750_751insG (p.His251Alafs*19) in exon 2, c.2604delC (p.Pro868Profs*5) in exon 11, and c.3077 T > A (p.Phe1026Tyr) in exon 14. Our results of the mutations associated with Wilson disease might facilitate the development of effective treatment plans.
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http://dx.doi.org/10.1186/s12881-018-0619-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006946PMC
June 2018

Comparative Genomic Analysis for Genetic Variation in Sacbrood Virus of Apis cerana and Apis mellifera Honeybees From Different Regions of Vietnam.

J Insect Sci 2017 Sep;17(5)

Molecular Microbiology Lab, Institute of Biotechnology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.

Sacbrood virus (SBV) is one of the most common viral infections of honeybees. The entire genome sequence for nine SBV infecting honeybees, Apis cerana and Apis mellifera, in Vietnam, namely AcSBV-Viet1, AcSBV-Viet2, AcSBV-Viet3, AmSBV-Viet4, AcSBV-Viet5, AmSBV-Viet6, AcSBV-Viet7, AcSBV-Viet8, and AcSBV-Viet9, was determined. These sequences were aligned with seven previously reported complete genome sequences of SBV from other countries, and various genomic regions were compared. The Vietnamese SBVs (VN-SBVs) shared 91-99% identity with each other, and shared 89-94% identity with strains from other countries. The open reading frames (ORFs) of the VN-SBV genomes differed greatly from those of SBVs from other countries, especially in their VP1 sequences. The AmSBV-Viet6 and AcSBV-Viet9 genome encodes 17 more amino acids within this region than the other VN-SBVs. In a phylogenetic analysis, the strains AmSBV-Viet4, AcSBV-Viet2, and AcSBV-Viet3 were clustered in group with AmSBV-UK, AmSBV-Kor21, and AmSBV-Kor19 strains. Whereas, the strains AmSBV-Viet6 and AcSBV-Viet7 clustered separately with the AcSBV strains from Korea and AcSBV-VietSBM2. And the strains AcSBV-Viet8, AcSBV-Viet1, AcSBV-Viet5, and AcSBV-Viet9 clustered with the AcSBV-India, AcSBV-Kor and AcSBV-VietSBM2. In a Simplot graph, the VN-SBVs diverged stronger in their ORF regions than in their 5' or 3' untranslated regions. The VN-SBVs possess genetic characteristics which are more similar to the Asian AcSBV strains than to AmSBV-UK strain. Taken together, our data indicate that host specificity, geographic distance, and viral cross-infections between different bee species may explain the genetic diversity among the VN-SBVs in A. cerana and A. mellifera and other SBV strains.
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http://dx.doi.org/10.1093/jisesa/iex077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634237PMC
September 2017

Three Novel Mutations in the Gene in Vietnamese Patients with Congenital Nephrotic Syndrome.

Case Rep Genet 2017 14;2017:2357282. Epub 2017 Mar 14.

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

Congenital nephrotic syndrome, a rare and severe disease, is inherited as an autosomal recessive trait. The disease manifests shortly after birth and occurs predominantly in families of Finnish origin but has now been observed in all countries and races. Mutations in the gene, which encodes nephrin, are the main causes of congenital nephrotic syndrome in patients. In this study, we report the first mutational analysis of the gene in three unrelated children from three different Vietnamese families. These patients were examined and determined to be suffering from congenital nephrotic syndrome in the Department of Pediatrics, Vietnam National Hospital of Pediatrics. All 29 exons and exon-intron boundaries of were analyzed by PCR and DNA sequencing. Genetic analysis of the gene revealed one compound heterozygous variant p.Glu117Lys, one heterozygous missense mutation p.Asp310Asn, and one heterozygous frame-shifting mutation (c.3250_3251insG causing p.Val1084Glyfs⁎12) in patient 1. In patient 2, one heterozygous variant p.Glu117Lys and one novel heterozygous missense mutation p.Ser324Ala were identified. Finally, a novel missense mutation p.Arg802Leu and a novel nonsense mutation (c.2442C>G causing p.K792⁎) were identified in patient 3.
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http://dx.doi.org/10.1155/2017/2357282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368377PMC
March 2017

A novel homozygous mutation IVS6+5G>T in CYP11B1 gene in a Vietnamese patient with 11β-hydroxylase deficiency.

Gene 2015 Jul 22;565(2):291-4. Epub 2015 Apr 22.

Institute of Genome Research, Vietnam Academy of Science and Technology, Vietnam. Electronic address:

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease which is characterized by a deficiency of one of the enzymes involved in the synthesis of cortisol from cholesterol by the adrenal cortex. CAH cases arising from impaired 11β-hydroxylase are the second most common form. Mutations in the CYP11B1 gene are the cause of 11β-hydroxylase deficiency. This study was performed on a patient with congenital adrenal hyperplasia and with premature development such as enlarged penis, muscle development, high blood pressure, and bone age equivalent of 5 years old at 2 years of chronological age. Biochemical tests for steroids confirmed the diagnosis of CAH. We used PCR and sequencing to screen for mutations in CYP11B1 gene. Results showed that the patient has a novel homozygous mutation of guanine (G) to thymine (T) in intron 6 (IVS6+5G>T). The analysis of this mutation by MaxEntScan boundary software indicated that this mutant could affect the gene splicing during transcription.
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http://dx.doi.org/10.1016/j.gene.2015.04.052DOI Listing
July 2015
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