Vietnamese Patient Research Articles

Detection of an EDA mutation causing hypohidrotic ectodermal dysplasia in a Vietnamese patient

Hypohidrotic ectodermal dysplasia (HED) is a rare disease characterized by abnormal development of the structures derived from the ectoderm layer, including hair, teeth, nails, and sweat glands. The most observed form of HED, which is known as X-linked hypohidrotic ectodermal dysplasia (XLHED), is commonly attributed to genetic abnormalities in the ectodysplasin A (EDA) gene. We have successfully discovered a known mutation c.1045G>A (p.A349T) in a Vietnamese proband who displayed the main symptoms of XLHED using PCR and Sanger sequencing. Furthermore, the segregation of the mutation showed that the mother, who exhibited a normal phenotype, was a carrier of the mutation, while the father was hemizygous for the wild-type allele. The identification of the mutation c.1045G>A (p.A349T) contributes to HED research worldwide and can be used for genetic counseling in Vietnam.

Whole exome sequencing identifies variants in the \(\textit{TNNI3}\) gene in vietnamese patient with restrictive cardiomyopathy - a case report

Restrictive cardiomyopathy (RCM) is a rare heart muscle disease in which the heart wall is rigid leading to diastolic dysfunction caused by abnormal elastic properties of the myocardium and/or intercellular matrix. The prognosis is generally poor, and RCM has a high mortality rate in pediatric patients. There are no curative treatments for RCM, so cardiac transplantation is the only effective treatment. Diagnosis RCM, clinical diagnosis can be challenging because clinical presentations and imaging manifestations of RCM are similar to other cardiomyopathies so it requires other specific diagnoses. Currently, pathogenic mutations in 22 different genes have been identified in patients with RCM. Identifying mutations in these genes helps discriminate RCM from other cardiomyopathies. Besides, next-generation sequencing (including whole genome sequencing, whole exome sequencing,...) has provided an effective tool for simultaneously analyzing mutations in many different genes. In this study, we conducted sequencing of the entire gene coding region (WES) in the patient and identified a compound heterozygote variants (c.289C>G, p.Arg97Gly and c.433C>T, p.Arg145Trp) in the TNNI3 gene. These variants were inherited from the patient's father and mother, who were heterozygous variant carriers. These variants were also identified as the pathogenic variants in the ClinVar database (accession number VCV001331910.2 and VCV000012426.28, respectively) and were the cause of the patient's disease. Our results suggest that WES can be used to definitively diagnose the genetic variants associated with RCM and show that genetic screening is essential for families of RCM patients.

Genomic insights into an extensively drug-resistant and hypervirulent Burkholderia dolosa N149 isolate of a novel sequence type (ST2237) from a Vietnamese patient hospitalised for stroke

Burkholderia dolosa is a clinically important opportunistic pathogen in inpatients. Here we characterised an extensively drug-resistant and hypervirulent B. dolosa isolate from a patient hospitalised for stroke. Resistance to 41 antibiotics was tested with the agar disc diffusion, minimum inhibitory concentration, or broth microdilution method. The complete genome was assembled using short-reads and long-reads and the hybrid de novo assembly method. Allelic profiles obtained by multilocus sequence typing were analysed using the PubMLST database. Antibiotic-resistance and virulence genes were predicted in silico using public databases and the 'baargin' workflow. B. dolosa N149 phylogenetic relationships with all available B. dolosa strains and Burkholderia cepacia complex strains were analysed using the pangenome obtained with Roary. B. dolosa N149 displayed extensive resistance to 31 antibiotics and intermediate resistance to 4 antibiotics. The complete genome included three circular chromosomes (6 338 630 bp in total) and one plasmid (167 591 bp). Genotypic analysis revealed various gene clusters (acr, amr, amp, emr, ade, bla and tet) associated with resistance to 35 antibiotic classes. The major intrinsic resistance mechanisms were multidrug efflux pump alterations, inactivation and reduced permeability of targeted antibiotics. Moreover, 91 virulence genes (encoding proteins involved in adherence, formation of capsule, biofilm and colony, motility, phagocytosis inhibition, secretion systems, protease secretion, transmission and quorum sensing) were identified. B. dolosa N149 was assigned to a novel sequence type (ST2237) and formed a mono-phylogenetic clade separated from other B. dolosa strains. This study provided insights into the antimicrobial resistance and virulence mechanisms of B. dolosa.

Molecular characterization of methicilin-resistant Staphylococcus aureus strain BM85 isolated from a Vietnamese patient with bloodstream infection

Methicillin-resistant Staphylococcus aureus (MRSA) is a threat to global health due to its resistance to β-lactam antibiotics and many other antibiotic classes developed via both intrinsic and acquired mechanisms. In this study, molecular characteristics related to antibiotic resistance of MRSA strain BM85 were investigated by whole-genome sequencing of a sample isolated from a patient with bloodstream infection at Bach Mai Hospital, Vietnam. Antibiotic susceptibility testing was also performed to determine the correlation between the presence of antibiotic-resistant genes and resistance phenotypes. Genomic analyses showed that the MRSA strain BM85 belonged to the major community-acquired (CA)-MRSA lineage ST59 originating from Taiwan. The strain harbored Staphylococcal Cassette Chromosome mec (SCCmec) type Vb (5C2&5) and Panton-Valentine leukocidin (PVL). Additionally, MRSA strain BM85 also possessed various antibiotic-resistant genes including tet38, tetK, blaZ, mecA, aph(3')-IIIa, aacA-aphD, and ermB which were located on mobile genetic elements MESPM1, Tn553-Tn4001 transposon, and a plasmid carrying the tetK gene, which was responsible for tetracycline resistance. The genotypic-resistant results were concordant with the phenotypic-resistant profile in which MRSA strain BM85 was resistant to penicillin, cefoxitin, gentamicin, kanamycin, tobramycin, erythromycin, and tetracycline. The sequencing data for the MRSA strain BM85 was deposited in GenBank, NCBI under accession number: BioProject PRJNA857185. In conclusion, the acquisition of the foreign genetic elements associated with antibiotic resistances through horizontal gene transfer mechanisms was the key driver of multidrug resistance in the multidrug-resistant MRSA strain BM85.

Establishment of cancer cell line originating from a patient with high-grade serous ovarian carcinoma.

Ovarian cancer is a serious malignancy with high prevalence and mortality. We isolated and characterized an ovarian high-grade serous cancer cell line (M4) from a tumor of a Vietnamese patient with ovarian carcinoma. The M4 cancer cell line showed good proliferation and stability in culture. Morphologically, the M4cells showed similar characteristics to tumor cells such as a polyhedral shape, large irregular nuclei, high nuclear/cytoplasmic ratio, high nuclear density and expressing cancer markers like CA125, p53 and Ki67markers. We have successfully isolated and characterized the M4 cell line from a Vietnamese patient with ovarian carcinoma.

A nonsense mutation in BRCA1 gene in a Vietnamese patient with breast cancer

Breast cancer is the most frequent female cancer, and it is increasing at an alarming rate. The typical symptom of breast cancer is breast lumps or swellings, though they can also develop close to the breast or under the arm. Breast cancer usually spreads to distant organs such as the bone, liver, lungs, and brain. Approximately 95% of breast cancer patients who arrive with the early-stage disease show no macroscopic signs of metastases. Although it is possible to reduce some breast cancer risks through prevention, the majority of patients in low-income countries are detected at a late stage. Because of this, even though current therapy is improving, early diagnosis is still crucial for improving the quality of treatment and the survival rate. Sex, age, family history, and an unhealthy lifestyle are some of the risk factors that may increase the chances of getting this disease. Familial or hereditary breast cancer accounts for 10% of breast cancers. Mutations in the BRCA1 and BRCA2 genes were responsible for 50% of all familial or hereditary breast cancer cases. In this research, mutations in a Vietnamese patient with familial breast cancer were analyzed using whole exome sequencing. As a result, 17 variants have been reported in the ClinVar database as “germline mutations” in familial breast cancer were detected. Of these, a heterozygous nonsense mutation c.5314C>T (p.R1772X) in the BRCA1 gene was identified as the genetic cause of this case. This mutation has been previously reported as pathogenic in the ClinVar database (ClinVar variation ID: 55480). Our results provide insight into the genetic causes of breast cancer as well as support the genetics diagnosis of familial breast cancer.

Autologous hematopoietic stem cell transplantation to treat systemic lupus erythematosus: The first case in Vietnam

Background: Systemic lupus erythematosus (SLE) is a chronic disease that causes systemic inflammation which affects multiple organs. There is no cure for SLE. Conventional treatment options include antimalarial drugs, corticosteroids, and immune suppressants, but a number of patients are resistant to treatment or suffer from severe side effects. Stem cell transplantation has been used to treat SLE for the past 2 decades. We describe the first Vietnamese patient with refractory SLE who received an autologous hematopoietic stem cell transplant. Case presentation: The patient is a woman who was diagnosed 12 years ago with systemic lupus erythematosus. She was administered corticosteroids and high-dose immunosuppressive medicines, but the condition was refractory, manifesting as severe headache, arthralgia, chronic anemia, severe Cushing's syndrome, and proteinuria. At admission, the SLEDAI score was 28 and proteinuria was 6.7g/l. She received cyclophosphamide and G-CSF for HSCT mobilization. Peripheral blood stem cells were collected and selected for CD34+ cells. Antithymocyte, cyclophosphamide, and rituximab were used in conditioning regimens. The patient was then administered a CD34+ autologous hematopoietic stem cell transfusion with a CD34+ dose of 7.93 x 106 cells/kg body weight, T and B lymphocyte purity of the graft exceeded 99.99%. Post-transplant course was favorable, the patient did not experience serious complications. Recovery of neutrophils on post-HSCT day +9 and platelet on day +12. Six months after stem cell transplantation, the patient's clinical symptoms significantly improved, the SLEDAI score dropped from 28 to 0, and the patient discontinued receiving immunosuppressive drugs. Conclusion: Autologous hematopoietic stem cell transplantation promises to be a new, effective therapeutic method that can be implemented more broadly in Vietnam for SLE patients.

Concordance of Clinical, Histologic and Direct Immunofluorescence Findings in Patients with Autoimmune Bullous Dermatoses in Vietnam.

Introduction: Autoimmune bullous dermatoses (ABD) represent a heterogeneous group of blistering disorders that may be debilitating with high morbidity. Clinical, histological, and direct immunofluorescence (DIF) studies are essential in establishing an accurate diagnosis of ABD, which is essential for its clinical management. Our study objective was to perform a systematic evaluation of ABD cases in a patient population at an academic medical center in Ho Chi Minh City, Vietnam, and determine the degree of concordance of clinical, histological, and DIF findings in ABD. Methodology: A systematic retrospective cross-sectional study was performed on 92 patients diagnosed with ABD by clinical, histological, and DIF studies at the University of Medicine and Pharmacy in Ho Chi Minh City, Vietnam, between September 2019 and September 2021. The clinical histories, H and E stained tissue sections, and DIF stains were evaluated by pathologists at the University of Medicine and Pharmacy. Results: ABD was evaluated as a whole and subdivided into an intraepidermal blister subgroup and a subepidermal blister subgroup. The analysis of paired diagnostic methods (clinical, histological, and DIF) for concordance with the final diagnosis was performed and showed that there were no statistically significant differences between the paired methods (McNemar’s test, p > 0.05). There was moderate concordance between the clinical, histological, and DIF diagnoses among all ABD cases (Brennan-Prediger coefficient Kappa test, κBP = 0.522, CI = 0.95). In the intraepidermal blister subgroup, the diagnostic accuracies of the histology and DIF stains were comparable to each other, and both were more accurate than a clinical diagnosis alone. In the subepidermal blister subgroup, there was no statistically significant difference in each pair of the three diagnostic methods (clinical, histological, and DIF) (McNemar’s test, p > 0.05). The concordance between the clinical, histological, and DIF diagnoses was high for the intraepidermal blister subgroup (Kappa test, κBP = 0.758, CI = 0.95). However, the concordance between the clinical, histological, and DIF diagnoses was slight for the subepidermal blister subgroup (Kappa test, κBP = 0.171, CI = 0.95). Conclusion: Histological evaluation is highly accurate in the diagnosis of the intraepidermal blister subgroup, but it is not as accurate in the diagnosis of the subepidermal blister subgroup in the Vietnamese patient cohort in which clinical, histological, and DIF studies were performed. DIF stains are a crucial diagnostic tool for ABD in this patient population.

Assessment of morphological and hemodynamic changes in adult atrial septal defect before and after percutaneous trans-catheter closure: the initial result in Vietnamese patient.

This study aimed to evaluate the change of morphology and hemodynamics in a relatively large number of patients with atrial septal defect (ASD) and provide the initial result in Vietnamese patients. This longitudinal, prospective case-control study was done at the Vietnam National Heart Institute from January 2012 to December 2017. The participants were divided into two groups: the ASD group, which included patients with ASDs, and the control group, which included healthy individuals or individuals without cardiac-related disorders. There were 94 participants in the ASD group and 83 participants in the control group. Most patients with ASDs in the study group were female, and the average age was 38.65 ± 14.8. The success rate of the ASD group was 98.9%. The right ventricle morphology and function showed right ventricular diameter, pulmonary trunk gradually decreased, FAC and ET increased, IVCT and IVRT decreased, and Tei index gradually decreased after each examination. Morphology and function of the left ventricle after ASD closure showed that the left ventricular diameter gradually increased, and EF% in 3 months after ASD closure increased statistically significantly. IVCT, IVRT, and LV Tei index decreased, and ET increased statistically significantly. After six months from ASD closure, the proportion of patients with NYHA I was 90.3%, with no patient with NYHA IV, and pulmonary vascular resistance gradually decreased. Percutaneous trans-catheter closure in Vietnamese adult atrial septal defect was an effective technique. Ventricle morphological and hemodynamic abnormalities following closure recovered statistical significance over time, particularly in the left ventricle.

Persistent Sciatic Artery: A Case Report

Persistent sciatic artery (PSA) is a very rare congenital vascular anomaly, occurs in 0.025% to 0.04% of the population, and occasionally associated with thromboembolic events or aneurismal diseases. We herein share experience of diagnosis and successful treatment of a Vietnamese patient with PSA complicated with distal thromboembolism. A 70-year-old woman was admitted to the hospital for acute lower limb ischemia. A computed tomography angiography (CTA) revealed complete occlusion of the left common iliac artery. Surgical embolectomy was carried out and abnormal distal left femoral artery was noted intraoperatively. Postoperative CTA showed a persistent sciatic artery (PSA) on the left and adequate perfusion of the left lower limb. During 2 years follow-up, the patient remained symptom-free with good perfusion to the distal left popliteal artery, anterior and posterior tibial arteries.

Detection of c.G2194A mutation in \(\textit{AR}\) gene of a vietnamese patient with androgen insensitivity syndrome: a case report

Androgen insensitivity syndrome (AIS) is a rare X-linked recessive androgen receptor (AR) disorder. However, the overlap in clinical manifestations between AIS and other disorders of sex development can cause clinical diagnostic difficulties. Applying the whole coding region sequencing method is an optimal method for the diagnosis of AIS. In this study, whole-exome sequencing was performed to screen mutations in the AR gene as well as genes related to disorders of sex development (DSD). Sanger sequencing was applied to validate the mutations in the patient. One missense mutation in the AR gene which was reported previously was identified in the patient. In this site, nucleotide G is changed to A at position 2194 on cDNA (c.G2194A), leading to a substitution of aspartic at position 732 aspartic to asparagine (p.Asp732Asn). However, this is the first published case in a Vietnamese with this mutation. Our study expands the mutation spectrum of the AR gene in Vietnamese patients and confirms the usefulness of whole-exome sequencing in the diagnosis of AIS. The results of the study are the basis for supporting doctors in prenatal diagnosis and giving reasonable advice to patients and families.

Whole-exome sequencing revealed a novel ERCC6 variant in a Vietnamese patient with Cockayne syndrome

We describe a case of Cockayne syndrome without photosensitivity in a Vietnamese family. This lack of photosensitivity prevented the establishment of a confirmed medical clinical diagnosis for 16 years. Whole-exome sequencing (WES) identified a novel missense variant combined with a known nonsense variant in the ERCC6 gene, NM_000124.4: c.[2839C>T;2936A>G], p.[R947*;K979R]. This case emphasizes the importance of WES in investigating the etiology of a disease when patients do not present the complete clinical phenotypes of Cockayne syndrome.

Whole-exome sequencing as a diagnostic tool for ipex syndrome

Immune dysregulation-Polyendocrinopathy-Enteropathy-X-linked (IPEX) syndrome is a life-threatening congenital autoimmune disorder caused by mutations in the forkhead box protein 3 (FOXP3) gene. Typical clinical manifestations of IPEX patients are early onset of intractable diarrhea, type 1 diabetes mellitus, and skin diseases. However, other autoimmune types such as severe food allergies, autoimmune cytopenias, autoimmune respiratory illness, and mesangial glomerulonephritis may complicate IPEX diagnosis. In this study, we report a Vietnamese 1-year-old boy with IPEX syndrome due to a hemizygous missense mutation, c.1190G>A (p.Arg397Gln), in exon 12 of the FOXP3 gene (NM_014009.4). The child had dermatitis, diarrhea, respiratory infections, and splenomegaly. The patient's serum routine test results were expected, except for white blood cells and neutrophils were higher than the normal, while IgA concentration was slightly below the normal range. However, he got no signal of diabetes or failure to thrive. Whole exome sequencing was applied to identify a genetic variant, and variant validation was examined using Sanger sequencing. The patient’s genetic mutation was inherited from his mother, an obligate carrier. His father had a normal genotype. This study is the first report of IPEX syndrome in a Vietnamese patient with a mutation in the FOXP3 gene detected by WES. This study provides further evidence for the role of mutations in the FOXP3 gene in patients with IPEX syndrome and demonstrates the need for genetic counselling and prenatal testing. Our results also show that WES sequencing is an effective tool in diagnosing genetic diseases.

A homozygous variant in G6PC in a Vietnamese patient with glycogen storage disease type Ia

Glycogen storage diseases (GSDs) are rare inherited metabolic disorders characterized by the absence of required enzymes for the glycogen degradation metabolism. GSD can be divided into more than 12 types based on enzyme deficiency and affected tissues, in which glycogen storage disease type Ia (GSD1a or von Gierke disease) is a liver-affecting form. GSD1a is an autosomal recessive inherited disease caused by mutations in the G6PC gene on chromosome 17q21. The present study reports a Vietnamese family with a 6-month-old male patient diagnosed with type Ia glycogen storage disease. A homozygous variant in the G6PC gene (NM_000151.3: c.518T>C; p.L173P) was detected in the proband using a comprehensive glycogen storage disease panel. This variant has been previously reported in ClinVar (Accession ClinVar: VCV000640818.3). The segregation of the variant was confirmed in ten people of a 3-generation family using Sanger sequencing. The results showed both parents were heterozygous for the variant. In addition, the variant c.518T>C in the G6PC gene was predicted to be deleterious using in silico prediction tools (SIFT, PolyPhen-2, Proven, REVEL, and MutPred2). Our results could help doctors decide on appropriate treatment and diet for the disease. Moreover, the study is also a contribution to molecular studies on GSD1a.

Comparative Genomic Analysis of the Human Variant of Methicillin-Resistant Staphylococcus aureus CC398 in Japan and Korea.

Staphylococcus aureus clonal complex (CC) 398 is a major clonal type of livestock-associated methicillin-resistant S. aureus and comprise both a human variant and a livestock-associated variant. We have previously identified three sequence type (ST) 1232 strains from Japanese patients (THI2018-120 and N1195) and a Vietnamese patient (S36). In this study, we found an ST1232 strain in a Korean patient (BDH17) and compared the genomes of the ST1232 strains isolated in Korea and Japan. Whole-genome sequencing and a phylogenetic tree based on single nucleotide polymorphisms showed that all ST1232 strains were human variants of S. aureus CC398 and were similar to a common lineage of Southeast Asia. All strains carried ϕSa2, ϕSa3, and Tn554, which included Panton-Valentine leukocidin, immune evasion cluster, and antimicrobial resistance genes, respectively. THI2018-120 and N1195 carried slightly different staphylococcal cassette chromosome mec element from BDH17 due to the insertion of a IS30 family. In addition, the strains originating from Japanese patients possessed a unique genetic element, blaZ-Tn4001-Tn554 element. In this study, we found that the ST1232 strains isolated in Korea and Japan are genetically closely related to each other. However, presence of the unique genetic elements suggests that the strains originating from Japanese patients may have evolved independently in Japan.

Encephalomalacia/gliosis, deep venous thrombosis, and cancer in Arg393His antithrombin Hanoi and the potential impact of the β-amyloid precursor protein (APP) on thrombosis and cancer.

A heterozygous Arg393His point mutation at the reactive site of antithrombin (AT) gene causing thrombosis in a Vietnamese patient is reported and named as Arg393His in AT-Hanoi. The present variant is characterized by a severe reduction of functionally active AT plasma concentration to 42% of normal resulting in multiple severe thrombotic events such as cerebral venous thrombosis (CVT) (encephalomalacia/gliosis), recurrent deep venous thrombosis (DVT) and the development of kidney cancer. Today the complexity of thrombophilia has grown with appreciation that multiple inherited and acquired risk factors may interact to result in a clinically thrombotic phenotype. This article focuses on the following issues: (1) pathophysiology and clinical conditions of Arg393His in AT-Hanoi; (2) “two way association” between cancer and thrombosis in which venous thromboembolism (VTE) can be both a presenting sign and a complication of cancer; (3) efficacy of anticoagulants used for the prevention of cancer-related thrombosis; (4) conditions of acquired risk factors such as cancer or genetic disorders via epigenetic modifications in gene-gene (epistasis) and/or gene-environment interactions such as in Lesch-Nyhan disease (LND), in which the β-amyloid precursor protein (APP) that may interact to predispose a patient to thrombosis and cancer. It is also necessary to study the hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme, AT, and APP using expression vectors for exploring their impact on LND, thrombosis as well as other human diseases, especially the ones related to APP such as Alzheimer's disease (AD) and cancer. For such a purpose, the construction of expression vectors for HGprt and APP, with or without the glycosyl-phosphatidylinositol (GPI) anchor, was performed as described in Ref. #148 (Nguyen, K. V., Naviaux, R. K., Nyhan, W. L. Lesch-Nyhan disease: I. Construction of expression vectors for hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme and amyloid precursor protein (APP). Nucleosides Nucleotides Nucleic Acids 2020, 39: 905–922). In the same manner, the construction of expression vectors for AT and APP can be performed as shown in Figure 6. These expressions vectors, with or without GPI anchor, could be used as tools for (a) studying the effects of Arg393His mutation in AT; (b) studying the emerging role of Arg393His mutation in AT and cancer; (c) studying intermolecular interactions between APP and AT.Furthermore, the construction of expression vectors as described in Ref. #148, especially the one with GPI, can be used as a model for the construction of expression vectors for any protein targeting to the cell plasma membrane for studying intermolecular interactions and could be therefore useful in the vaccines as well as antiviral drugs development (studying intermolecular interactions between the spike glycoprotein of the severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, as well as its variants and the angiotensin-converting enzyme 2, ACE2, in coronavirus disease 2019 (COVID-19) [155],[156], for example).

Whole exome sequencing revealed a large deletion in EDAof a Vietnamese patient with hypohidrotic ectodermal dysplasia

Hypohidrotic ectodermal dysplasia (HED) (OMIM # 305100) is a congenital genetic disorder caused by mutations in EDA (NM_001399) on chromosome X. Children with HED have the abnormal development of epidermal structures such as skin, hair, nails, teeth, and sweat glands. The present study aimed to detect mutations in EDA of a Vietnamese family with a son having only five teeth and no sweat glands, using whole exome sequencing (WES) and multiplex PCR. The results showed that patient had a deletion of exon 1 in EDA (c.2_396del), which is likely to be inherited from the healthy mother. The results will partly contribute to molecular studies on HED, helping in genetic counseling and disease treatment.

IDENTIFICATION OF MALASSEZIA SPECIES AND ITS ASSOCIATION WITH CLINICAL MANIFESTATIONS OF ATOPIC DERMATITIS

Introduction: Atopic dermatitis is a chronic, recurrent inflammatory skin disease that is characterized by an eczematous reaction. Few studies have investigated fungi in the pathogenesis of atopic dermatitis, however, there are different about distribution of Malassezia species. Objectives: To indentificate of Malassezia species and its asociation with clinical manifestations in Vietnamese atopic dermatitis patient. Methods: 178 patients who were diagnosed with atopic dermatitis and had a postitive direct examination of Malassezia at the National hospital of dermatology and venereology between July 2019 and June 2020. Specimens were taken with cellotape, then stained in 20% of potassium hydroxit combined with ParkerTM blue black ink. All patient who had postive test were cultured on SDA and mDixon. For fungal samples, we selected pure colonies with morphological characteristics of yeast as follows about 1cm in diameter, round, cream or milky in color, smooth and glossy to detect the species. Results: From the samples of atopic dermatitis patients, we cultured and idenfified 41 cases. 5 species were found, in which M. globosa was the most common species, accounting for 39%, followed by M. restricta (19.5%), M. dermatis (17.1%), M. furfur (17.1%) and M. sympodialis (2.4%). Conclusion: On the skin lesions of Vietnamese patients with atopic dermatitis, M. globosa was the most common species with 39.0%.

Identification of a de novo mutation in KRT5 gene underlying epidermolysis bullosa simplex by whole exome sequencing in a Vietnamese patient

Epidermolysis bullosa simplex (EBS) is a group of epidermolysis bullosa (EB) and accounts for 75-85% EB cases. Most EBS patients are caused by mutations in KRT5 or KRT14, encoding for keratin 5 and keratin 14, respectively, which impair the structural entirety of paired intermediate filaments expressed in the fracture of basal keratinocytes and subsequent blistering of the epithelium. This study aimed to identify the causative mutation in a Vietnamese EB case. Whole exome sequencing (WES) was performed in the affected individual and revealed a de novo heterozygous pathogenic mutation in exon 7 of KRT5 gene, resulting in an amino acid change at position 477, with glutamic acid to lysine substitution (p.E477K). The KRT5 p.E477K was strong associated with the very severe or lethal of generalized severe EBS (GS-EBS), characterized by the severe symptoms at birth, improving with age and evolution to palmoplantar keratoderma and nail dysplasia. Our finding will aid the molecular diagnosis, prognosis prediction of the patient with GS-EBS due to p.E477K and significant genetic counselling the family concerning the recurrence risk for future pregnancies.

Identification of c.199-10T>G mutation in SLC25A20 gene related to fatty acid oxidation disorders on a Vietnamese patient

Fatty acid oxidation disorders (FAODS) consist of rare diseases which affect the energy production of the mitochrondria by disrupting the β-oxidation of fatty acid, resulting in energy deficiency and toxic acumulation in the patient’s body. Typical clinical symtoms of FAODS include rhabdomyolysis, myoglobinuria, cardiomyopathy, hypoketotic hypoglycemia and liver dysfunction on the newborns and could lead to mortality in most of the cases. Mutations occur in different genes in the enzymatic pathway of the mitochrondria may cause diffirent types of FAODS.The objective of this study was to screen and identify genetic mutations associated with fatty acid oxidation disorders in Vietnamese patients through whole exome sequencing analysis. The result revealed a reported homozygous c.199-10T>G mutation in the position of 10 nucleotides before the exon 3 of the SLC25A20 gene. The SLC25A20 gene encodes the carnitine acylcarnitine translocase (CACT), which plays an important role in transporting acylcarnitine and carnitine in the mitochondria. Genetic mutations in this gene often lead to carnitine-acylcarnitine translocase deficiency (CACTD) - a rare form of FAODs. By in silico analysis, the c.199-10T>G mutation was predicted as a splite site mutation that could lead to exon skipping during the creation of mature mRNA. Genetic analysis of the patient’s family showed that both parents had the mutation c.199-10T>G in heterozygous form. This result suggests that every mutant allele in the patient is inherited from parents. Our finding not only improved our understanding of the c.199-10T>G mutation in SLC25A20 gene of our patient but also provides important information for future research, diagnosis and genetic counseling of FAOS in Vietnamese patients.