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BACKGROUND: WAS gene mutational analysis is crucial to establish a definite diagnosis of Wiskott-Aldrich syndrome (WAS). Data on the genetic background of WAS in Vietnamese patients have not been reported. METHODS: We recruited 97 male, unrelated patients with WAS and analyzed WAS gene mutation using Sanger sequencing technology. RESULTS: We identified 36 distinct hemizygous pathogenic mutations, with 17 novel variants, from 38 patients in the entire cohort (39.2%). The mutational spectrum included 14 missense, 12 indel, five nonsense, four splicing, and one non-stop mutations. Most mutations appear only once, with the exception of c.37C>T (p.R13X) and c.374G>A (p.G125E) each of which occurs twice in unrelated patients. CONCLUSION: Our data enrich the mutational spectrum of the WAS gene and are crucial for understanding the genetic background of WAS and for supporting genetic counseling.
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Síndrome de Wiskott-Aldrich , Humanos , Masculino , Análisis Mutacional de ADN , Mutación , Vietnam , Síndrome de Wiskott-Aldrich/diagnóstico , Síndrome de Wiskott-Aldrich/genética , Proteína del Síndrome de Wiskott-Aldrich/genéticaRESUMEN
BACKGROUND: Thalassemias are common inherited blood disorders that have been extensively studied in Asia. Thus far, data on mutations of the HBB gene in Vietnamese patients with ß-thalassemia are limited to small studies. METHODS: We recruited 696 ß-thalassemia patients and carriers in southern Vietnam and analyzed for the HBB gene mutations using Sanger sequencing technology. RESULTS: We documented 27 types of known mutations and 10 types of novel variants on 737 alleles out of 1392 surveyed alleles. The three most common mutations, which account for more than ¾ of all mutant alleles, were c.79G > A (HbE), c.124_127delTTCT, and c.52A > T. The novel variants were mainly located in 5' untranslated region (c.-92delC and c.-67A > G) and 3' untranslated region (c.*4C > T, c.*116_*117insA, c.*142 T > C, c.*156G > C, c.*176_*177insA, and c.*247 T > C), except for one in intron 2 (c.316-99 T > G) and one in exon 3 (c.385delG). CONCLUSION: We provide here a comprehensive mutation spectrum of the HBB gene in Southern Vietnam, which is crucial for carrier screening and prenatal diagnosis in the future.
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Globinas beta , Talasemia beta , Alelos , Femenino , Genotipo , Humanos , Mutación/genética , Embarazo , Vietnam/epidemiología , Globinas beta/genética , Talasemia beta/genéticaRESUMEN
6-mercaptopurine (6-MP) plays a critical role in the treatment of pediatric acute lymphoblastic leukemia (ALL). NUDT15 and TPMT gene variants have been strongly associated with myelotoxicity caused by using 6-MP. Therefore, the purpose of this study is to investigate the frequency of NUDT15 and TPMT polymorphisms, as well as the impact of NUDT15 variants on the use of 6-MP to treat pediatric ALL in Vietnam. Sanger sequencing was applied to detect NUDT15 and TPMT gene variants in 70 pediatric ALL patients. Duration of drug interruption, level of neutropenia, and 6-MP tolerance dose were recorded. NUDT15 variants were detected from 23 out of 70 (32.9%) patients. Three well-known haplotype variants were identified as NUDT15 *2 (p.V18_V19insGV and p.R139C), *3 (p.R139C), and *6 (p.V18_V19insGV); besides, a novel NUDT15 p.R11Q was not previously reported. The NUDT15 wild-type, heterozygous variant, and homozygous variant genotypes were 67.1%, 30.1%, and 2.8%, respectively. Two TPMT heterozygous polymorphisms were TPMT*3C and *6, accounted for 2.8%. Patients with intermediate and low activity NUDT15 were given the median 6-MP tolerance dose of 55.2 and 37.2 versus 69.5 mg/m2/day of patients with NUDT15 normal activity (p = 0.0001). Patients with homozygous variant diplotype were drastically sensitive to 6-MP, with an average dose intensity of 49.6%, compared to 73.6% and 92.7% of those with heterozygous and wild-type diplotype, respectively (p = 0.0001). Our results suggest that 6-MP dose adjustment should be based on NUDT15 variants in pediatric Vietnamese ALL patients.
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Mercaptopurina , Metiltransferasas/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras , Pirofosfatasas/genética , Antimetabolitos Antineoplásicos/efectos adversos , Pueblo Asiatico , Niño , Humanos , Mercaptopurina/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pirofosfatasas/uso terapéutico , VietnamRESUMEN
We report a case of calcium pyrophosphate dihydrate deposition disease (CPDD) involving a patient on maintenance hemodialysis (MHD). The 32-year-old man presented in August 2016 with a complaint of left shoulder swelling of 8 months' duration with no trauma or fever. He was diagnosed with nephrotic syndrome in 1998, which progressed to ESRD. He commenced MHD in 2012. Examination at our hospital revealed a soft nontender swelling of the left shoulder. Blood biochemistry showed elevated serum urate, phosphate, ß2 microglobulin, and parathyroid hormone. Imaging revealed joint effusion and dense heterogenous deposition. Aspirate analysis showed urate crystals 3+, and culture yielded no growth. Following rheumatology review, the working diagnosis was periarticular tissue tuberculosis, after excluding pseudogout and amyloidosis. Following 1 month of colchicine and allopurinol, synovial fluid microscopy showed CPDD crystals. Symptoms gradually resolved over the course of 6 months. In this rare case, a diagnosis of CPDD was made with a multidisciplinary approach that included imaging and biochemical investigations.
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Alopurinol/administración & dosificación , Enfermedades Óseas Metabólicas , Condrocalcinosis , Colchicina/administración & dosificación , Fallo Renal Crónico , Síndrome Nefrótico , Diálisis Renal/efectos adversos , Adulto , Enfermedades Óseas Metabólicas/sangre , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Enfermedades Óseas Metabólicas/etiología , Condrocalcinosis/sangre , Condrocalcinosis/tratamiento farmacológico , Condrocalcinosis/etiología , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Masculino , Síndrome Nefrótico/sangre , Síndrome Nefrótico/terapia , VietnamRESUMEN
In recent years, considerable progress has been made in the standard treatment for chronic lymphocytic leukaemia (CLL) due to the availability of new potent drugs. However, the majority of data on CLL were derived from Western populations, with limited studies and guidelines on the management of CLL from an Asian population perspective. This consensus guideline aims to understand treatment challenges and suggest appropriate management approaches for CLL in the Asian population and other countries with a similar socio-economic profile. The following recommendations are based on a consensus by experts and an extensive literature review and contribute towards uniform patient care in Asia.
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Leucemia Linfocítica Crónica de Células B , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/epidemiología , Leucemia Linfocítica Crónica de Células B/terapia , Asia/epidemiologíaRESUMEN
BACKGROUND: The cytogenetic characteristics are important factors for risk stratification at diagnosis of acute myeloid leukemia (AML); however, cytogenetic profile of Vietnamese patients with AML remains undetermined. In this study, we present the chromosomal data of de novo AML patients in Southern Vietnam. METHODS: We performed cytogenetic testing for 336 AML patients using G banding. If the patients had suspected abnormalities, fluorescence in situ hybridization with probes of inv(3)(q21q26)/t(3;3)(q21;q26), 5q31, 7q31, t(8;21)(q21.3;q22), 11q23, t(15;17)(q24;q21), inv(16)(p13q22)/t(16;16)(p13;q22)were analyzed. Patients without above aberrations or with normal karyotype were tested by fluorescence in situ hybridization using probe 11q23. RESULTS: We found that the median age was 39 years. According to French - American - British classification, AML-M2 is the most frequent type with 35.1%. Chromosomal abnormalities were detected in 208 cases, accounting for 61.9%. Among structural abnormalities, t(15;17) was the most common (19.6%), followed by t(8;21) and inv (16)/t(16;16) in 10.1% and 6.2%, respectively. In perspective of chromosomal numerical abnornmalities, loss of sex chromosomes are the most common (7.7%), followed by +8 in 6.8%, -7/del(7q) in 4.4%, +21 in 3.9% and -5/del (5q) in 2.1%. The prevalence of addditional cytogenetic aberrations accompanying with t(8;21) and inv(16)/t(16;16) were 82.4% and 52.4%, repectively. None of +8 cases was associated with t(8;21). Regarding cytogenetic risk assessment according to European Leukemia Net 2017, there were 121 (36%) patients in favorable-risk, 180 (53.6%) in intermediate-risk and 35 (10.4%) in adverse-risk group. CONCLUSION: In conclusion, this is the first comprehensive cytogenetic profile of Vietnamese patients diagnosed with de novo AML, which helps clinical doctors in prognostic classification for AML patients in Southern Vietnam.
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Leucemia Mieloide Aguda , Translocación Genética , Humanos , Adulto , Translocación Genética/genética , Hibridación Fluorescente in Situ , Vietnam/epidemiología , Aberraciones Cromosómicas , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnósticoRESUMEN
INTRODUCTION: The prevalence of gene mutations in hemophagocytic lymphohistiocytosis (HLH) varied between studies. Thus far, data on the genetic background of HLH in Vietnamese patients are limited. METHODS: We recruited 94 HLH patients and analyzed for the 4 genes using Sanger sequencing technology. RESULTS: Pathogenic variants were observed in 36 (38.29%) patients, including 27 in UNC13D, 5 in STXBP2, 3 in PRF1, and 2 in STX11 (one patient with digenic variants in both UNC13D and STX11). Monoallelic variants accounted for 77.8% of all cases with mutation. A total of 23 different types of pathogenic variants were documented in the 4 genes tested, including 15 in UNC13D, 3 in PRF1, 3 in STXBP2, and 2 in STX11. Interestingly, the novel splicing variant c.3151G>A in UNC13D was recurrently identified in 8 unrelated patients. CONCLUSION: Vietnamese patients with HLH showed a distinct genetic variant spectrum, in which UNC13D is the predominant genetic lesion associated with HLH.
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Biomarcadores , Linfohistiocitosis Hemofagocítica/genética , Proteínas de la Membrana/genética , Proteínas Munc18/genética , Mutación , Perforina/genética , Proteínas Qa-SNARE/genética , Alelos , Empalme Alternativo , Análisis Mutacional de ADN , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , VietnamRESUMEN
Background: The picture of Vietnamese patients with essential thrombocythemia (ET) remains mostly undetermined. Our study intended to determine the frequency of JAK2V617F, CALR exon 9, and MPL exon 10 mutations as well as to analyze clinical characteristics associated with different mutational status in Vietnamese ET patients. Methods: We explored mutations of JAK2V617F, MPL, and CALR from 395 patients using allele specific oligonucleotide polymerase chain reaction and Sanger sequencing techniques; then, the clinical and hematological features were compared according to mutation patterns. Results: We found that JAK2V617F, CALR exon 9, and MPL exon 10 mutations were present in 56.2%, 27.6%, and 1% of the 395 patients with ET, respectively. Twelve different types of CALR mutation were detected in 109 patients, with the CALR type 1 mutation (c.1099_1150del; L367fs*46) was the most common, followed by CALR type 2 mutation (c.1154_1155insTTGTC; K385fs*47). The JAK2V617F-positive patients had older age, higher white blood cell counts and higher hemoglobin levels but lower platelet counts than patients with CALR mutations or patients negative for triple tests. There was no significant difference regarding sex ratio, white blood cell counts, platelet counts and hemoglobin levels among CALR mutation subtypes. Conclusion: we reported high frequency of JAK2V617F, CALR, and MPL mutations in Vietnamese patients with ET and underscored the importance of combined genetic tests for diagnosis and classification of ET into different subtypes.
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Calreticulina/genética , Janus Quinasa 2/genética , Mutación , Receptores de Trombopoyetina/genética , Trombocitemia Esencial/genética , Trombocitemia Esencial/patología , Adulto , Anciano , Femenino , Estudios de Seguimiento , Pruebas Hematológicas , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Trombocitemia Esencial/epidemiología , Vietnam/epidemiologíaRESUMEN
Recently, large deletions adjacent to the Philadelphia (Ph) translocation breakpoint on the derivative chromosome 9 have been reported to be found in a substantial number of patients with chronic myelogenous leukemia (CML). The existence of der(9) deletion is reported as a powerful indicator of a poor prognosis. So far, der(9) deletion is considered to be generated when the Ph translocation occurs, because when der(9) deletion is found, it is detected in all the Ph-positive (Ph+) cells of a particular CML patient. On FISH examination of 47 Vietnamese CML patients, we found 11 patients carrying der(9) deletion. Among these, two patients harbored Ph+ metaphase cells with der(9) deletion and also Ph+ cells without it. In CML patients with der(9) deletion, reportedly no ABL/BCR transcript is detected. In these two patients, the proportion of Ph+ cells without der(9) deletion was much smaller than that of the cells with der(9) deletion. Nevertheless, we detected a ABL/BCR (1b-b4) transcript in the two patients. This is further evidence for the existence of Ph+ cells without der(9) deletion. It is possible that in some CML patients, der(9) deletion is generated in the progression of the disease.
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Deleción Cromosómica , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Adulto , Aberraciones Cromosómicas , Proteínas de Fusión bcr-abl/genética , Humanos , Hibridación Fluorescente in Situ , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Masculino , Persona de Mediana EdadRESUMEN
Adipose-derived stem cells (ADSCs) have been put forward as promising therapeutics for end-stage liver disease (ESLD). In the present study, we compared the effects of defined chemicals and liver extract on the hepatic differentiation of ADSCs. ADSCs were isolated according to the method described in our previously published study. Subsequently, the differentiation of ADSCs was induced separately by chemicals (including hepatic growth factor (HGF), fibroblast growth factor (FGF), and oncostatin M (OSM)) and liver extract (30 µg/ml) in a total period of 21 d. The efficiency of hepatic differentiation was evaluated by changes in the cell morphology, gene expression, and cellular function. The results showed that the liver extract promoted the hepatic differentiation of ADSCs to a significantly greater extent than the chemicals. In the group of ADSCs treated with liver extract, changes in the cell morphology began sooner, and the expression of alpha-FP and albumin genes was higher than that in the chemically treated group. The ADSCs in both the groups stained positive for anti-alpha trypsin (AAT) and albumin markers. The cells also exhibited glycogen storage capacity. Therefore, we concluded that the liver extract could efficiently induce the differentiation of ADSCs into hepatocyte-like cells. This study reveals the potential of mesenchymal stem cell differentiation in the liver extract, which supports further preclinical and clinical research on the application of ADSCs in ESLD treatment.