Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.309
Filtrar
1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 33-36, 2020 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-31922592

RESUMO

OBJECTIVE: To explore hematological and genotypic characteristics of patients with hemoglobin E (Hb E) disorders from Yunnan Province. METHODS: One hundred individuals with Hb E disorders indicated by high performance liquid chromatography (HPLC) were subjected to genetic testing through multiple gap-PCR and reverse dot-blotting analysis. RESULTS: All patients were found to harbor a mutation to the 26th codon of the ß -globin chain (HBB: c.79G>A). Ninety patients were heterozygotes, and 10 co-inherited c.79G>A and an α -thalassemia mutation (7 α α /-α3.7, 2 α α /--SEA and 1 -α 3.7/-α3.7). Hematological characteristics of the heterozygotes were: Hb A2 (26.02±3.64)%, Hb F(1.35±1.25)%, MCV(78.83±4.68) fl, MCH(26±1.54) pg, MCHC (329.65±10.73) g/L, HGB (141.08±16.53) g/L, while that of the co-inherited cases was decided by the type of α -thalassemia mutation. CONCLUSION: Hb E can be effectively detected by HPLC. The type of α -thalassemia mutations will determine hematological features of co-inherited cases. Hb E disorders may be missed by relying only on routine blood test upon prenatal screening.


Assuntos
Hemoglobina E , Talassemia alfa , China , Feminino , Genótipo , Hemoglobina E/genética , Humanos , Mutação , Gravidez , Talassemia alfa/genética , Globinas beta/genética
2.
Expert Opin Investig Drugs ; 29(1): 23-31, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31847604

RESUMO

Introduction: Sickle cell disease (SCD) is caused by a mutation in the HBB gene which is key for making a component of hemoglobin. The mutation leads to the formation of an abnormal hemoglobin molecule called sickle hemoglobin (HbS). SCD is a chronic, complex disease with a multiplicity of pathophysiological targets; it has high morbidity and mortality.Hydroxyurea has for many years been the only approved drug for SCD; hence, the development of new therapeutics is critical.Areas covered: This article offers an overview of the key studies of new therapeutic options for SCD. We searched the PubMed database and Cochrane Database of Systemic Reviews for agents in early phase clinic trials and preclinical development.Expert opinion: Although knowledge of SCD has progressed, patient survival and quality of life must be improved. Phase II and phase III clinical trials investigating pathophysiology-based novel agents show promising results in the clinical management of SCD acute events. The design of long-term clinical studies is necessary to fully understand the clinical impact of these new therapeutics on the natural history of the disease. Furthermore, the building of global collaborations will enhance the clinical management of SCD and the design of primary outcomes of future clinical trials.


Assuntos
Anemia Falciforme/tratamento farmacológico , Desenvolvimento de Medicamentos , Hidroxiureia/uso terapêutico , Anemia Falciforme/genética , Anemia Falciforme/fisiopatologia , Animais , Humanos , Mutação , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Globinas beta/genética
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1130-1132, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703143

RESUMO

OBJECTIVE: To analyze the hematological characteristics of a patient with Hb Ottawa in conjunction with ß -thalassemia. METHODS: Peripheral blood samples from the proband and her parents were collected and subjected to red blood cell analysis and hemoglobin electrophoresis. Genotypes of α - and ß -globin genes were also analyzed. RESULTS: The proband and her mother were both heterozygotes for Hb Ottawa and ß -thalassemia variant IVS II-654, and presented with typical ß -thalassemia trait featuring hypochromic microcytic anemia. An abnormal hemoglobin band was detected upon electrophoresis. CONCLUSION: Co-existence of Hb Ottawa and ß -thalassemia may not aggravate the phenotype.


Assuntos
Hemoglobinas Anormais/genética , Talassemia beta/genética , Feminino , Testes Genéticos , Heterozigoto , Humanos , alfa-Globinas/genética , Globinas beta/genética
4.
Nat Commun ; 10(1): 4479, 2019 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578323

RESUMO

Hematopoietic stem cell (HSC) gene therapy is being evaluated for hemoglobin disorders including sickle cell disease (SCD). Therapeutic globin vectors have demanding requirements including high-efficiency transduction at the HSC level and high-level, erythroid-specific expression with long-term persistence. The requirement of intron 2 for high-level ß-globin expression dictates a reverse-oriented globin-expression cassette to prevent its loss from RNA splicing. Current reverse-oriented globin vectors can drive phenotypic correction, but they are limited by low vector titers and low transduction efficiencies. Here we report a clinically relevant forward-oriented ß-globin-expressing vector, which has sixfold higher vector titers and four to tenfold higher transduction efficiency for long-term hematopoietic repopulating cells in humanized mice and rhesus macaques. Insertion of Rev response element (RRE) allows intron 2 to be retained, and ß-globin production is observed in transplanted macaques and human SCD CD34+ cells. These findings bring us closer to a widely applicable gene therapy for hemoglobin disorders.


Assuntos
Anemia Falciforme/terapia , Terapia Genética/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/metabolismo , Lentivirus/genética , Globinas beta/genética , Anemia Falciforme/genética , Animais , Antígenos CD34/metabolismo , Vetores Genéticos/genética , Humanos , Macaca mulatta , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Reprodutibilidade dos Testes , Transplante Heterólogo , Globinas beta/metabolismo
6.
BMC Med Genet ; 20(1): 136, 2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399060

RESUMO

BACKGROUND: Thalassemia is the most common inherited disease in the world, involving α- or ß-globin in red blood cells. Thalassemia cases rank fifth in the list of national catastrophic diseases in Indonesia; however, nationwide screening for thalassemia carriers is not yet mandatory. This study aimed to assess whether blood count metrics, such as the Shine & Lal index (SLI; MCV*MCV*MCH/100), might serve as a predictor to screen thalassemia carriers in a limited resource area where molecular methods are not readily available. METHODS: During a family gathering of thalassemia patients, family members (n196) underwent a complete blood count test. Those with MCV < 80 fL and/or MCH < 27 pg and/or SLI < 1530 were further examined for Hb analysis. Only samples with HbA2 fraction > 4% or with a peak in the HbE fraction were sequenced to confirm ß-globin gene mutations. RESULTS: Of 196 family members, 117 (59.6%) had low MCV and/or low MCH and/or low SLI. The HbE fraction (mean 24.06% ± 0.95, range 22.4-26.5) was found in 27 (13.7%) cases, and all had a mutation at codon (CD)26 (c.79G > A). The mean HbA2 fraction in these samples was 3.18% ± 0.62 (range 2.6-3.8). For samples with HbA2 > 4% (n30; 15.3%), all had mutations at IVS1nt5 (c.92 + 5 G > C; n28), CD8/9 (c.27_28insG; n1) and CD19 (c.59A > G; n1). The mean HbA2 fraction with a mutation at IVS1nt5 (c.92 + 5 G > C) was 4.65% ± 0.77 (range 4.0-5.6). Interestingly, anaemia was only present in 25 and 57% of ß-thalassemia carriers with mutations at CD26 (c.79G > A) and at IVS1nt5 (c.92 + 5 G > C), respectively. CONCLUSIONS: The Shine & Lal index is helpful in the early screening of ß-thalassemia carriers, since this index confirms mutations at CD-26 (c.79G > A) and at IVS1nt5 (c.92 + 5 G > C), which are both common mutations in Bandung, Indonesia. Further DNA analysis is a topic of interest to map variants in globin genes and their distribution across populations.


Assuntos
Diagnóstico Precoce , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Globinas beta/genética , Talassemia beta/genética , Adolescente , Sequência de Bases , Eritrócitos , Feminino , Hemoglobinas/genética , Humanos , Indonésia , Masculino , Deleção de Sequência
7.
Yi Chuan ; 41(8): 669-676, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31447418

RESUMO

ß-thalassemia (ß-thal) is a fatal and disabling inherited blood disorder with diverse phenotypes. The same or similar genotype of ß-thal can manifest variable clinical severities. It is the hotspot and emphasis in the field of hematopathy and genetic diseases to explore genetic modifiers that influence the phenotype of ß-thal. This review illustrates the deteriorating and amelioratig modifiers from two aspects: genotypes of α-globin and quantitative trait locus of fetal hemoglobin (Hb F). Variations of transcription factors which reactive the γ-globin gene expression and ß-globin cluster cis-acting elements were introduced emphatically. Finally, clinical applications and future development prospects of ß-thal genetic modifiers are introduced by examples.


Assuntos
Talassemia beta/genética , Hemoglobina Fetal/genética , Genótipo , Humanos , Fenótipo , Fatores de Transcrição/genética , alfa-Globinas/genética , Globinas beta/genética , gama-Globinas/genética
8.
Hemoglobin ; 43(2): 126-128, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31304856

RESUMO

Congenital erythrocytosis is a rare and hereditary disorder of red blood cell (RBC) production that can be caused by high oxygen affinity hemoglobin (Hb) variants. We applied a genetic approach including whole exome sequencing and Sanger sequencing. We identified a heterozygous ß-globin gene (Hb San Diego or HBB: c.328G>A) in exon 3 as a causative germline mutation in a Chinese family with congenital erythrocytosis. We concluded that in erythrocytosis with a dominant inheritance and normal or inappropriately high erythropoietin (EPO) levels, the high oxygen affinity Hb variants should be considered. In addition, as a tool for identification of mutations in congenital erythrocytosis, whole exome sequencing improves diagnostic accuracy and provides the opportunity for discovery of novel variants.


Assuntos
Hemoglobinas Anormais , Policitemia/genética , Globinas beta/genética , Grupo com Ancestrais do Continente Asiático , Eritropoetina/metabolismo , Família , Mutação em Linhagem Germinativa , Humanos , Oxigênio/metabolismo , Policitemia/congênito , Sequenciamento Completo do Exoma
9.
Cell Mol Biol (Noisy-le-grand) ; 65(5): 49-53, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31304906

RESUMO

The aim of the present study was to investigate the correlation between human papillomavirus (HPV) type 6/11 and 16/18 infections and glandular thickening mammary gland hyperplasia in order to explore methods for preventing glandular thickening mammary gland hyperplasia. A total of 240 patients with glandular thickening mammary gland hyperplasia who were treated by surgery in our hospital from January 2012 to June 2017 were enrolled in the present study. The hyperplastic breast tissue and adjacent normal breast tissue were taken to test HPV type 6/11 and 16/18 infections using conventional PCR and in situ hybridization techniques. The correlations between HPV type 6/11 and 16/18 infections and glandular thickening mammary gland hyperplasia were analyzed using statistical methods of chi-square test. The infection rates of HPV type 6/11 and 16/18 in the hyperplastic breast tissue were 31.95% and 34.91%, respectively and 11.83% and 14.79% in the normal breast tissue, respectively. The differences were statistically significant (all p<0.05). HPV type 6/11 and 16/18 infections may be closely related to the development of glandular thickening mammary gland hyperplasia, and may be one of the causes of glandular thickening mammary gland hyperplasia.


Assuntos
Papillomavirus Humano 11/genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Hiperplasia/virologia , Glândulas Mamárias Humanas/patologia , Infecções por Papillomavirus/patologia , Distribuição de Qui-Quadrado , DNA Viral/genética , Feminino , Humanos , Hiperplasia/prevenção & controle , Hiperplasia/cirurgia , Hibridização In Situ , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Globinas beta/genética
10.
J Pak Med Assoc ; 69(7): 959-963, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31308562

RESUMO

OBJECTIVE: To find frequency ofalpha Thalsaemia nhomozygous beta Thalsaemia patients, and to se any difernce infrequency and age ofirst ransfusion and mean haemoglobin concentration. METHODS: The single-centred, escriptive cros-sectional study was conducted athe National Instiute of Blod Disease and Bone Marow Transplantaion, Karchi, from June 1,2012, to May 31, 2013. Patients of homozygous beta halsaemia, diagnosed by polymerase chain reaction, wer tested for coinheritance of alpha Thalsaemia nd foetal haemoglobin XMN1 polymorphism using polymerase chain reaction. SPS 17 was used for dat anlysi. RESULTS: Of the 286 patients, 19(41.6%) wer males, and 9(34.6%) showed coinheritance ofalpha thalsaemia. In the coinheritance group, 50(50%) and 1(1%) patients recived 1-20 and 21-40 times transfusions per year espectively, while inthe non-coinheritance group, the coresponding numbers wer 125(67%) and 27(14.%). Overal, 73(25.%) patients had nevr ben transfused, including 38(13.%) patients inthe alpha Thalsaemia group. XMN1 polymorphism was found in 86(41%) ofthe 208 patients who wer tested and anlysed on this count. CONCLUSIONS: Alpha thalsemia was presnt inmore than one-third homozygous beta halsemia patients.


Assuntos
Talassemia alfa/epidemiologia , Talassemia beta/epidemiologia , Adolescente , Transfusão de Sangue , Criança , Pré-Escolar , Comorbidade , Feminino , Homozigoto , Humanos , Lactente , Recém-Nascido , Masculino , Paquistão/epidemiologia , alfa-Globinas/genética , Talassemia alfa/sangue , Talassemia alfa/genética , Talassemia alfa/terapia , Globinas beta/genética , Talassemia beta/sangue , Talassemia beta/genética , Talassemia beta/terapia
11.
Hemoglobin ; 43(2): 145-147, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31268351

RESUMO

More than 900 abnormal hemoglobin (Hb) ß chain variants have now been characterized. The majority are due to point mutations resulting in a single amino acid substitution within the globin gene involved, with nearly twice as many ß chain variants identified compared to α chain variants. Although most of these variants are clinically and hematologically silent, they can interact with different thalassemia mutations, which could sometimes render laboratory diagnostics in a routine setting difficult. In this study, we present a case of coinheritance of Hb City of Hope [ß69(E13)Gly→Ser; HBB: c.208G>A] and ß-thalassemia (ß-thal), that compromises the molecular diagnosis of ß-thal trait.


Assuntos
Códon/genética , Hemoglobinas Anormais/genética , Mutagênese Insercional , Patologia Molecular/métodos , Globinas beta/genética , Talassemia beta/diagnóstico , Hemoglobinopatias/genética , Heterozigoto , Humanos
12.
Anal Bioanal Chem ; 411(29): 7669-7680, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31273412

RESUMO

There is a general agreement that pharmacologically mediated stimulation of human γ-globin gene expression and increase of production of fetal hemoglobin (HbF) is a potential therapeutic approach in the experimental therapy of ß-thalassemia and sickle cell anemia. Here, we report the development and characterization of cellular biosensors carrying enhanced green fluorescence protein (EGFP) and red fluorescence protein (RFP) genes under the control of the human γ-globin and ß-globin gene promoters, respectively; these dual-reporter cell lines are suitable to identify the induction ability of screened compounds on the transcription in erythroid cells of γ-globin and ß-globin genes by FACS with efficiency and reproducibility. Our experimental system allows to identify (a) HbF inducers stimulating to different extent the activity of the γ-globin gene promoter and (b) molecules that stimulate also the activity of the ß-globin gene promoter. A good correlation does exist between the results obtained by using the EGFP/RFP clones and experiments performed on erythroid precursor cells from ß-thalassemic patients, confirming that this experimental system can be employed for high-throughput screening (HTS) analysis. Finally, we have demonstrated that this dual-reporter cell line can be used for HTS in 384-well plate, in order to identify novel HbF inducers for the therapy of ß-thalassemia and sickle cell anemia. Graphical abstract.


Assuntos
Técnicas Biossensoriais , Diferenciação Celular/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Ensaios de Triagem em Larga Escala/métodos , Regiões Promotoras Genéticas , Transcrição Genética , Globinas beta/genética , gama-Globinas/genética , Eritrócitos/citologia , Hemoglobina Fetal/genética , Proteínas de Fluorescência Verde/genética , Humanos , Células K562 , Reprodutibilidade dos Testes
13.
Biomed Res Int ; 2019: 9210841, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275994

RESUMO

Beta-thalassemia is described as a group of hereditary blood disorders characterized by abnormalities in the synthesis of beta chains of hemoglobin. These anomalies result in different phenotypes ranging from moderate to severe clinical symptoms to no symptoms at all. Most of the defects in hemoglobin arise directly from the mutations in the structural ß-globin gene (HBB). Recent advances in computational tools have allowed the study of the relationship between the genotype and phenotype in many diseases including ß-thalassemia. Due to high prevalence of ß-thalassemia, these analyses have helped to understand the molecular basis of the disease in a better way. In this direction, a relational database, named HbVar, was developed in 2001 by a collective academic effort to provide quality and up-to-date information on the genomic variations leading to hemoglobinopathies and thalassemia. The database recorded details about each variant including the altered sequence, hematological defects, its pathology, and its occurrence along with references. In the present study, an attempt was made to investigate nondeletion mutations in the HBB picked up from HbVar and their effects using the in silico approach. Our study investigated 12 nucleotides insertion mutations in six different altered sequences. These 12 extra nucleotides led to the formation of a loop in the protein structure and did not alter its function. It appears that these mutations act as 'silent' mutations. However, further in vitro studies are required to reach definitive conclusions.


Assuntos
Biologia Computacional/métodos , Mutação/genética , Globinas beta/química , Globinas beta/genética , Talassemia beta/genética , Sequência de Bases , Humanos , Simulação de Dinâmica Molecular , Conformação Proteica
14.
Hemoglobin ; 43(2): 132-136, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31190580

RESUMO

We report four cases of compound heterozygotes for Hb S (HBB: c.20A>T) and a rare ß0-thalassemia (ß0-thal) mutation, Hb Westdale (HBB: c.380_396delTGCAGGCTGCCTATCAG), characterized by a 17 bp deletion between codons 126 to 131 in exon 3 of the ß-globin gene of human hemoglobin (Hb) confirmed by direct ß-globin gene sequencing. All four cases were from four unrelated families belonging to the Agharia caste, an endogamous ethnic community of the Sundargarh and Jharsuguda districts of Odisha State, India. Detailed observations indicated that all four cases of Hb S/Hb Westdale were clinically severe. On family screening, six family members were found to be heterozygous for Hb Westdale and were asymptomatic. Deletional α-thalassemia (α-thal) and XmnI polymorphism were studied for all the Hb Westdale cases. The Hb S/Hb Westdale cases had an early median age at onset of symptoms and presentation, more requirement of blood transfusions, splenomegaly and hepatomegaly and were found to be clinically more severe when compared with the Hb S-ß-thal with IVS-I-5 (G>C) (HBB: c.92 + 5G>C) cases. Overall, the findings indicate that this rare and hitherto unreported compound heterozygosity of Hb S/Hb Westdale is a clinically significant hemoglobinopathy and its finding in a large endogamous community of Odisha State, India will have important implication in the epidemiology and understanding of the clinical spectrum of sickle cell disease in Indian context and prenatal diagnosis.


Assuntos
Hemoglobina Falciforme/genética , Hemoglobinopatias/etnologia , Hemoglobinas Anormais/genética , Heterozigoto , Mutação , Globinas beta/genética , Transfusão de Sangue , Hemoglobinopatias/genética , Hemoglobinopatias/patologia , Hemoglobinopatias/terapia , Hepatomegalia/etiologia , Humanos , Índia/etnologia , Polimorfismo de Nucleotídeo Único , Deleção de Sequência , Esplenomegalia/etiologia
15.
Nucleic Acids Res ; 47(15): 7955-7972, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31147717

RESUMO

Sickle cell disease (SCD) is a monogenic disorder that affects millions worldwide. Allogeneic hematopoietic stem cell transplantation is the only available cure. Here, we demonstrate the use of CRISPR/Cas9 and a short single-stranded oligonucleotide template to correct the sickle mutation in the ß-globin gene in hematopoietic stem and progenitor cells (HSPCs) from peripheral blood or bone marrow of patients with SCD, with 24.5 ± 7.6% efficiency without selection. Erythrocytes derived from gene-edited cells showed a marked reduction of sickle cells, with the level of normal hemoglobin (HbA) increased to 25.3 ± 13.9%. Gene-corrected SCD HSPCs retained the ability to engraft when transplanted into non-obese diabetic (NOD)-SCID-gamma (NSG) mice with detectable levels of gene correction 16-19 weeks post-transplantation. We show that, by using a high-fidelity SpyCas9 that maintained the same level of on-target gene modification, the off-target effects including chromosomal rearrangements were significantly reduced. Taken together, our results demonstrate efficient gene correction of the sickle mutation in both peripheral blood and bone marrow-derived SCD HSPCs, a significant reduction in sickling of red blood cells, engraftment of gene-edited SCD HSPCs in vivo and the importance of reducing off-target effects; all are essential for moving genome editing based SCD treatment into clinical practice.


Assuntos
Anemia Falciforme/terapia , Edição de Genes/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/metabolismo , Globinas beta/genética , Anemia Falciforme/genética , Animais , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Células Cultivadas , Eritrócitos/metabolismo , Terapia Genética/métodos , Humanos , Células K562 , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Resultado do Tratamento
16.
Hemoglobin ; 43(1): 23-26, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31146650

RESUMO

ß-Thalassemia (ß-thal) is the most frequently observed hereditary blood disorder that results from genetic defects causing deficient synthesis of hemoglobin (Hb) polypeptide chains. Detecting thalassemia mutations are necessary for prenatal diagnosis (PND) programs leading a better quality of life for the patients, as well as a reduction in the cost of their medical care. There are more than 900 different genomic mutations of the ß-globin gene described in the human hemoglobin variant (HbVar) database. In this study, we identified a mid-intronic mutation at IVS-II-821 (A>C) (HBB: c.316-30A>C) position in the HBB gene of an Iranian proband and two of her siblings that was associated with ß-thal clinical features. Direct DNA sequence analysis was performed by mutation scanning of the ß-globin gene. Based on the observed ß-thal phenotype and bioinformatics analysis results, we concluded that this ß-globin gene mutation was associated with a mild phenotype of ß-thal through activating potential splice sites by creating exonic splicing enhancers (ESEs), exon-identity element (EIE) and exonic splicing regulatory sequences (ESRs) sites.


Assuntos
Éxons , Íntrons , Mutação , Fenótipo , Globinas beta/genética , Talassemia beta/diagnóstico , Talassemia beta/genética , Adolescente , Adulto , Alelos , Índices de Eritrócitos , Feminino , Frequência do Gene , Humanos , Irã (Geográfico) , Masculino , Adulto Jovem , Talassemia beta/sangue
17.
Hemoglobin ; 43(2): 129-131, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31246535

RESUMO

We present the case of a novel ß-globin gene variant associated with early-onset transfusion-dependent anemia compatible with a ß-thalassemia major (ß-TM) phenotype in a patient of British descent. As a child, our patient developed chronic symptomatic anemia with hemoglobin (Hb) nadirs of 3.0 g/dL. She started receiving occasional transfusions by the age of 13 years and became transfusion-dependent by the age of 32 years. Work-up performed at our center showed a Hb electrophoresis compatible with ß-thalassemia (ß-thal) trait. Polymerase chain reaction (PCR) of the ß-globin gene detected a novel mutation situated at codon 110 (CTG). This missense mutation led to a substitution of the thymine nucleotide (nt) base for guanine (CGG) at position 332 (HBB: c.332T>G). We have named this new mutation Hb London-Ontario. The majority of previously described dominant allelic mutations of the ß-globin gene led to a ß-thal intermedia (ß-TI) phenotype. The heterozygous mutation which was detected in our patients is unique at it leads to a more severe ß-TM phenotype. We suspect this is a de novo mutation of which the mother of our patient, who was reported to have a form of thalassemia, was the proband.


Assuntos
Anemia/genética , Transfusão de Sangue , Hemoglobinas Anormais/genética , Mutação de Sentido Incorreto , Globinas beta/genética , Adolescente , Adulto , Anemia/terapia , Criança , Eletroforese , Feminino , Heterozigoto , Humanos , Fenótipo , Talassemia beta/diagnóstico
18.
Biomed Res Int ; 2019: 8702968, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205946

RESUMO

Similarity/dissimilarity analysis is a key way of understanding the biology of an organism by knowing the origin of the new genes/sequences. Sequence data are grouped in terms of biological relationships. The number of sequences related to any group is susceptible to be increased every day. All the present alignment-free methods approve the utility of their approaches by producing a similarity/dissimilarity matrix. Although this matrix is clear, it measures the degree of similarity among sequences individually. In our work, a representative of each of three groups of protein sequences is introduced. A similarity/dissimilarity vector is evaluated instead of the ordinary similarity/dissimilarity matrix based on the group representative. The approach is applied on three selected groups of protein sequences: beta globin, NADH dehydrogenase subunit 5 (ND5), and spike protein sequences. A cross-grouping comparison is produced to ensure the singularity of each group. A qualitative comparison between our approach, previous articles, and the phylogenetic tree of these protein sequences proved the utility of our approach.


Assuntos
Complexo I de Transporte de Elétrons/genética , Proteínas Mitocondriais/genética , Análise de Sequência de Proteína , Software , Globinas beta/genética , Complexo I de Transporte de Elétrons/química , Humanos , Proteínas Mitocondriais/química , Globinas beta/química
19.
Hemoglobin ; 43(1): 52-55, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31106603

RESUMO

This study reports the case of 2-year-old Northeastern Thai girl with ß-thalassemia (ß-thal) disease who has required regular blood transfusions since she was 8 months old. Hemoglobin (Hb) analysis by high performance liquid chromatography (HPLC) separated Hb A2/E (16.5%), Hb F (22.7%), Hb A (51.8%) and an abnormal peak (Hb X) found at a retention time (RT) of 5.05 min. (C-window) with 2.8%. Multiplex gap-polymerase chain reaction (gap-PCR) revealed heterozygous α-thalassemia-2 (α-thal-2) (-α3.7/αα; NG_000006.1: g.34164_37967 del3804). This patient was suspected of having a ß-globin chain variant and Hb E (HBB: c.79G>A) according to the high Hb F level and disease presentations. Surprisingly, Hb Mahasarakham (the geographic origin of the proband), a novel single nucleotide deletion (-G) at the first nucleotide of codon 121 (HBB: c.364delG), was identified by direct DNA sequencing and secondary confirmation by PCR-restriction fragment length polymorphism (PCR-RFLP). This novel mutation causes a frameshift mutation and added 10 more residues to the ß-globin chain that was elongated to 156 amino acids. Molecular basis of this novel mutation in the heterozygous state is required to confirm the mode of inheritance.


Assuntos
Heterozigoto , Mutação , Domínios Proteicos/genética , Talassemia alfa/diagnóstico , Talassemia alfa/genética , Globinas beta/genética , Alelos , Substituição de Aminoácidos , Sequência de Bases , Pré-Escolar , Análise Mutacional de DNA , Eritrócitos/patologia , Feminino , Hemoglobinas Anormais/genética , Humanos , Globinas beta/química
20.
Blood ; 133(21): 2245-2246, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31122935
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA