RESUMO
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.
Assuntos
Síndrome de Wiskott-Aldrich , Humanos , Masculino , Análise Mutacional de DNA , Mutação , Vietnã , Síndrome de Wiskott-Aldrich/diagnóstico , Síndrome de Wiskott-Aldrich/genética , Proteína da Síndrome de Wiskott-Aldrich/genéticaRESUMO
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.
Assuntos
Globinas beta , Talassemia beta , Alelos , Feminino , Genótipo , Humanos , Mutação/genética , Gravidez , Vietnã/epidemiologia , Globinas beta/genética , Talassemia beta/genéticaRESUMO
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.
Assuntos
Mercaptopurina , Metiltransferases/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras , Pirofosfatases/genética , Antimetabólitos Antineoplásicos/efeitos adversos , Povo Asiático , Criança , Humanos , Mercaptopurina/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pirofosfatases/uso terapêutico , VietnãRESUMO
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.
Assuntos
Alopurinol/administração & dosagem , Doenças Ósseas Metabólicas , Condrocalcinose , Colchicina/administração & dosagem , Falência Renal Crônica , Síndrome Nefrótica , Diálise Renal/efeitos adversos , Adulto , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/tratamento farmacológico , Doenças Ósseas Metabólicas/etiologia , Condrocalcinose/sangue , Condrocalcinose/tratamento farmacológico , Condrocalcinose/etiologia , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Síndrome Nefrótica/sangue , Síndrome Nefrótica/terapia , VietnãRESUMO
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.
Assuntos
Leucemia Linfocítica Crônica de Células B , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/epidemiologia , Leucemia Linfocítica Crônica de Células B/terapia , Ásia/epidemiologiaRESUMO
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.
Assuntos
Leucemia Mieloide Aguda , Translocação Genética , Humanos , Adulto , Translocação Genética/genética , Hibridização in Situ Fluorescente , Vietnã/epidemiologia , Aberrações Cromossômicas , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnósticoRESUMO
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.
Assuntos
Biomarcadores , Linfo-Histiocitose Hemofagocítica/genética , Proteínas de Membrana/genética , Proteínas Munc18/genética , Mutação , Perforina/genética , Proteínas Qa-SNARE/genética , Alelos , Processamento Alternativo , Análise Mutacional de DNA , Estudos de Associação Genética , Predisposição Genética para Doença , Testes Genéticos , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , VietnãRESUMO
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.
Assuntos
Calreticulina/genética , Janus Quinase 2/genética , Mutação , Receptores de Trombopoetina/genética , Trombocitemia Essencial/genética , Trombocitemia Essencial/patologia , Adulto , Idoso , Feminino , Seguimentos , Testes Hematológicos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Trombocitemia Essencial/epidemiologia , Vietnã/epidemiologiaRESUMO
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.
Assuntos
Deleção Cromossômica , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Adulto , Aberrações Cromossômicas , Proteínas de Fusão bcr-abl/genética , Humanos , Hibridização in Situ Fluorescente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Hepatopatias/terapia , Extratos Hepáticos/farmacologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Tecido Adiposo/citologia , Albuminas/biossíntese , Animais , Terapia Baseada em Transplante de Células e Tecidos/métodos , Células Cultivadas , Fatores de Crescimento de Fibroblastos/farmacologia , Glicogênio/metabolismo , Fator de Crescimento de Hepatócito/farmacologia , Humanos , Camundongos , Oncostatina M/farmacologia , alfa 1-Antitripsina/biossíntese , alfa-Fetoproteínas/biossínteseRESUMO
From 1990 to 2000, 513 cases of aplastic anemia were diagnosed and treated in Blood transfusion and Hematology Centre of Ho Chi Minh city, composing of 144 children and 369 adults with 279 males and 234 females. By bone marrow aspiration and biopsy, we diagnosed these cases as follow: aplastic anemia 449 cases (87.5%), hypocellularity of bone marrow: 45 (8.8%), one lignea hypocellularity of bone marrow: 19 (3.7%). From these cases, we have found that: - ’s difficult to point out accurately the cause of aplastic anemia and this is still the question for many studies in future. - All the patient was treated mainly blood transfusion, corticoid and androgen (77.5%) with complete and partial response was 25.5%. Besides, 32 cases were treated with corticoid + Sandimum given better results with complete response (32.7%).
Assuntos
Doenças da Medula Óssea , TerapêuticaRESUMO
This 29 years old woman was admitted to the hospital with menstrual and dental bleeding. Physical examination revealed a pale brust on the legs. Laboratory data. - Hemograme: Hb: 7.5 g/dl, Hct: 22.7%, RBC: 2.86 x 1012/ l, WBC: 57.109/l hemostatic: PT: 23“7 (10”9), INR 5.86, aPTT: 32” (38”), PT¬mix 11”2 (10”9). Dosage of factor VII: 2.7%. Dosage of factor X: 102%. Diagnosis: congenital factor VII deficiency. Treatment: frozen plasma (15 ml/kg/day x 3 days) and provera 10 mg/dayx 4 days.
Assuntos
Deficiência do Fator VIIRESUMO
From Feb 1997 to Feb 1998, 74 children with ITP, that diagnosed and treated for the first time (38 cas males, 36 cas females) at Centre of Blood Transfussion and Hematology, HCM City. Results of the treatment regimens corticosteroids 4mg/kg body weight/day and corticosteroids 2mg/kg body weight/day are noted: complete response (74.2%) partial response (9%), dependent of Corticosteroids (6.2%), persisstent thrombocytopenia (10.6%) and persistent ITP after 6 months (chronic ITP): 20.2%. With the treatment regimen 4mg/kg body weight/day, platelet counts increased to > 50.10 g/l in a median of 4+/- 0.85 days and the treatment regiment 2 mg/kg body weight/day, platelet counts incresed to > 50.10g/l in a median of 10+/- days (P< 0.001).