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1.
Augment Altern Commun ; 35(4): 285-298, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31884826

RESUMO

Some school-age children with multiple disabilities communicate predominately through the display of prelinguistic behaviors such as gestures, vocalizations, facial expressions, and eye gaze. Increasing the frequency and complexity of these behaviors may be one approach to building communication and transitioning toward linguistic communication (i.e., symbolic language). The current preliminary study used a single-subject ABB'B" design nested within a multiple baseline across participants design with randomization to evaluate a multi-phase intervention aimed at increasing social gaze behaviors. The participants were 5 school-age children with multiple disabilities. Participants appeared to demonstrate increases in both the frequency and complexity of their social gaze behavior during the intervention according to Improvement Rate Difference calculations that largely maintained four months after intervention ended. More research is needed, but the intervention shows promise as one aspect of AAC intervention for children who are prelinguistic communicators. Future research is critical to evaluating this or related interventions with a larger number of individuals and across a larger range of profiles and ages.


Assuntos
Auxiliares de Comunicação para Pessoas com Deficiência , Transtornos da Comunicação/reabilitação , Fixação Ocular , Comportamento Social , Paralisia Cerebral/reabilitação , Criança , Encefalomalacia/reabilitação , Expressão Facial , Feminino , Gestos , Humanos , Desenvolvimento da Linguagem , Masculino , Deficiência Intelectual Ligada ao Cromossomo X/reabilitação , Comunicação não Verbal , Talassemia alfa/reabilitação
2.
PLoS One ; 14(12): e0216020, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31830127

RESUMO

BACKGROUND: The diagnosis of sickle cell disease (SCD) is made by hemoglobin assays such as high-performance liquid chromatography (HPLC), isoelectric focusing and cellulose acetate or citrate agar electrophoresis. These assays are easy to perform and used in large-scale newborn screening in many countries. These tests however may not easily differentiate Sß0 thalassemia from SS or identify other hemoglobin variants, and in this case, hemoglobin (HBB) gene sequencing may be necessary. OBJECTIVES: To develop a high throughput DNA based confirmatory assay for SCD and to detect mutations in the HBB gene. METHODS: We developed an automated pyrosequencing technique (PyS) based on QIAGEN technology (Hilden, Germany) to detect homozygous or heterozygous hemoglobin S mutations as well as hemoglobin C mutations. The technique was tested on 2,748 samples from patients enrolled in a multi-center SCD cohort in Brazil. Patients were previously tested using HPLC to diagnose SCD as part of routine clinical care. Any subjects with discrepant results between HPLC and PyS or with heterozygous hemoglobin S detected had Sanger sequencing of the HBB gene. RESULTS: We identified 168 samples with discrepant results between HPLC and PyS and 100 with concordant PyS = heterozygous S and HPLC, which would suggest SB-thalassemia or other heterozygous S variants. The PyS assay correctly identified 1906 (98.7%) of the 1930 HbSS and 628 (98.7%) of the 636 HbSC samples. Of the 179 remaining samples, PyS correctly indicated S heterozygosis in 165 (92.2%). Of the 165 heterozygous S samples confirmed by Sanger as consistent with Sß thalassemia genotype, 84 samples were classified as Sß0 thalassemia and 81 as Sß+ thalassemia. The most frequent beta thalassemia mutations of Sß0 and Sß+ were HBB: c.118C>T (Gln40Stop) and HBB c.92 + 6T> C, respectively. DISCUSSION: The PyS proved to be satisfactory for large-scale confirmatory testing of hemoglobin mutation. Moreover, with this study we were able to describe the most common ß+ and ß0 mutations in SCD patients with Sß-thalassemia in a large multi-institutional SCD cohort in Brazil.


Assuntos
Anemia Falciforme/diagnóstico , Hemoglobina Falciforme/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Talassemia beta/diagnóstico , Anemia Falciforme/epidemiologia , Anemia Falciforme/genética , Brasil/epidemiologia , Estudos de Coortes , Genótipo , Humanos , Talassemia beta/epidemiologia , Talassemia beta/genética
3.
Sci Rep ; 9(1): 18610, 2019 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-31819078

RESUMO

Although the discrimination between ß-thalassemia trait (ßTT) and Iron deficiency anemia (IDA) is important clinically, but it is challenging and normally difficult; so if a patient with IDA is diagnosed as ßTT, then it is deprived of iron therapy. This study purpose was to evaluate the 26 different discriminating indices diagnostic function in patients with microcytic anemia by using accuracy measures, and also recommending two distinct new discriminating indices as well. In this study, 907 patients were enrolled with the ages over 18-year-old with either ßTT or IDA. Twenty-six discrimination indices diagnostic performance presented in earlier studies, and two new indices were introduced in this study (CRUISE index and index26) in order to evaluate the differential between ßTT and IDA by using accuracy measures. 537 (59%) patients with ßTT (299 (56%) women, and 238 (44%) men), and also 370 (41%) patients with IDA (293 (79%) women, and 77 (21%) men) were participated in this study for evaluating the 28 discrimination indices diagnostic performance. Two new introduced indices (CRUISE index and index26) have better performance than some discrimination indices. Indices with the amount of AUC higher than 0.8 had very appropriate diagnostic accuracy in discrimination between ßTT and IDA, and also CRUISE index has good diagnostic accuracy, too. The present study was also the first cluster analysis application in order to identify the homogeneous subgroups of different indices with similar diagnostic function. In addition, new indices that offered in this study have presented a relatively closed diagnostic performance by using cluster analysis for the different indices described in earlier studies. Thus, we suggest the using of cluster analysis in order to determine differential indices with similar diagnostic performances.


Assuntos
Anemia Ferropriva/diagnóstico , Testes Hematológicos/métodos , Talassemia beta/diagnóstico , Adolescente , Adulto , Idoso , Área Sob a Curva , Análise por Conglomerados , Estudos Transversais , Diagnóstico Diferencial , Índices de Eritrócitos , Feminino , Ferritinas , Hemoglobinas/análise , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
5.
Ann Hum Biol ; 46(7-8): 610-615, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31793346

RESUMO

Background: Consanguinity increases the incidence of recessive diseases such as beta-thalassaemia major (ßTM), one of the most prevalent lethal inherited diseases in the world.Aim: This study aims to identify the frequency of endogamy and consanguinity in two Mediterranean ßTM populations and to study the implication of socio-economic factors.Subjects and methods: A trans-sectional study was conducted in 203 Tunisian families and 75 Italian families. Data were collected using a questionnaire completed by patients and parents.Results: Complete endogamy and consanguinity were observed in 82.75% and 62.56% of Tunisian families, respectively. Complete endogamy was found in 90.67% of Italian families, no consanguinity was noted. The low occupation status of Tunisian mothers was associated with an increasing frequency of consanguinity (p = .01) and endogamy (p = .0003). Consanguinity was associated with low education level (p = .012) and low occupation status (p=.047) of fathers. No significant association was found between endogamy and socio-economic factors in the Italian sample.Conclusions: High consanguinity and endogamy rates in Tunisian families may explain the frequency of ßTM in Tunisia. The high endogamy rate in Italian families could also increase the frequency of ßTM. Identification of geographical distribution and socio-economic factors leading to endogamy and consanguinity in these populations might help to improve ßTM prevention.


Assuntos
Consanguinidade , Casamento/estatística & dados numéricos , Fatores Socioeconômicos , Talassemia beta/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Itália , Masculino , Tunísia , Adulto Jovem
7.
Ann Ist Super Sanita ; 55(4): 351-356, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850862

RESUMO

INTRODUCTION: Blood transfusion is a lifesaving procedure for patients affected by hematological diseases or hemorrhage risk. AIM: This retrospective study was aimed to evaluate clinical safety of pediatric transfusions by comparing the frequency of adverse events caused by apheretic blood components vs whole blood. METHODS: From 2011 to 2015, 214 patients (blood malignancy patients, n = 144 and thalassemic patients, n = 70) received 12 531 units of blood components. The adverse acute reactions occurred during patient hospitalization were reported to the Hemovigilance system and assessed by fitting a logistic mixed-effect model. RESULTS: A total of 33 (0.3%) adverse acute events occurred. Odds ratio (OR) of adverse events from apheresis vs whole blood transfusion adjusted by patient classification was not statistically significant (OR [95% CI], 0.75 [0.23-2.47]). CONCLUSION: Our findings showed no significant differences in the prevalence of adverse acute events between blood component collected by apheresis vs whole blood in our study center.


Assuntos
Transfusão de Sangue/estatística & dados numéricos , Reação Transfusional/epidemiologia , Adolescente , Remoção de Componentes Sanguíneos , Transfusão de Componentes Sanguíneos/efeitos adversos , Transfusão de Componentes Sanguíneos/estatística & dados numéricos , Segurança do Sangue , Transfusão de Sangue/métodos , Criança , Feminino , Neoplasias Hematológicas/terapia , Humanos , Modelos Logísticos , Masculino , Razão de Chances , Prevalência , Distribuição Aleatória , Estudos Retrospectivos , Talassemia/terapia , Adulto Jovem
8.
Hematol., Transfus. Cell Ther. (Impr.) ; 41(4): 316-323, Oct.-Dec. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1056238

RESUMO

ABSTRACT Background: Blood transfusion-transmitted infections in individuals suffering from beta-thalassemia have been reported in Pakistan, but the information on their sociodemographic and clinical determinants is lacking. This study aims to describe the prevalence, as well as the factors, contributing in blood transfusion-transmitted infections. Method: Between December 2011 and December 2013, in a non-probable sampling, 350 thalassemia patients were recruited in Lahore, Multan, Karachi and Peshawar, Pakistan. Subjects were screened for transfusion-transmitted infections. Results: A seropositive rate of 36.5% was observed; males (94, 73.4%) and females (34, 26.6%). Among several risk factors associated with transfusion-transmitted infections, province (p = 0.001), gender (p = 0.003), age (p < 0.03), education (p < 0.00), degree of consanguinity (p = 0.05), age at fetal blood test (p = 0.005), fetal hemoglobin levels (p = 0.005), death due to thalassemia (p = 0.001) and iron-related complications (p = 0.04) showed significant correlation. Participants with an age >10 years were significantly more prone to seropositivity than those aged ≤10 years. Moreover, the ferritin level was also significantly higher in those aged >10 years than in those ≤10 years. It was observed that males had a higher seroprevalence rate (94, 73.4%) than females (34, 26.6%). The most prevalent transfusion-transmitted infections was the hepatitis C virus, with 115 cases (89.8%). Conclusion: A high prevalence rate of HCV in subjects with transfusion-dependent thalassemia is linked with insufficient facilities, poor management and compromised socioeconomic status. Therefore, more multicenter studies covering cities from different regions of the country are needed in order to develop preventive measurements at the regional and national level.


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Paquistão , Talassemia , Estudos Soroepidemiológicos , Fatores de Risco , Hepacivirus , Reação Transfusional/epidemiologia
9.
Acta méd. costarric ; 61(4): 190-194, oct.-dic. 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1054731

RESUMO

Resumen En este reporte de caso se describe el primer paciente doble heterocigoto para alfa+-talasemia tipo -3,7 y rasgo heterocigoto por hemoglobina S en Costa Rica, diagnosticado desde su nacimiento por medio del tamizaje neonatal como heterocigoto para hemoglobina S. Luego de la detección de la hemoglobina S por tamizaje, el paciente fue referido al servicio de Hematología del Hospital Nacional de Niños para su seguimiento, en donde se observa hemograma con índices y morfología de glóbulos rojos sugestivos de alfa talasemia, con presentación de electroforesis de hemoglobina con patrón AS cuya expresión relativa de HbS era menor de lo esperado, lo que motivó a efectuar estudio molecular del gen de alfa globina, que confirmó el diagnóstico de alfa talasemia con deleción heterocigota de tipo -3,7 en herencia conjunta con la heterocigosis de hemoglobina S.


Abstract In this case report we describe the first patient compound heterozygous for type -3.7 alpha+ thalassemia and sickle cell trait in Costa Rica, who was diagnosed from birth by neonatal screening as heterozygous for hemoglobin S. After detection of hemoglobin S by screening, the patient was referred to the Hematology service of the National Children`s Hospital for follow-up, where hemogram with indexes and morphology of red blood cells suggestive of alpha thalassemia is observed, presenting hemoglobin electrophoresis with AS pattern whose relative expression of hemoglobin S was lower tan expected, which led to a molecular study of the alpha globin gene confirming the diagnosis of alpha thalassemia with heretozygous deletion of type -3.7, in co-inheritance with hemoglobin S heterozygosis.


Assuntos
Humanos , Masculino , Recém-Nascido , Hemoglobina A , Hemoglobina Falciforme , Triagem Neonatal , Talassemia alfa , Costa Rica , Hemoglobinopatias , Triagem de Portadores Genéticos
10.
Neuroimage Clin ; 24: 102058, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31711032

RESUMO

OBJECTIVE: Multisystem iron poisoning is a major concern for long-term beta-thalassemia management. Quantitative MRI-based techniques routinely show iron overload in heart, liver, endocrine glands and kidneys. However, data on the brain are conflicting and monitoring of brain iron content is still matter of debate. METHODS: This 3T-MRI study applied a well validated high-resolution whole-brain quantitative MRI assessment of iron content on 47 transfusion-dependent (mean-age: 36.9 ±â€¯10.3 years, 63% females), 23 non-transfusion dependent (mean-age: 29.2 ±â€¯11.7 years, 56% females) and 57 healthy controls (mean-age: 33.9 ±â€¯10.8 years, 65% females). Clinical data, Wechsler Adult Intelligence Scale scores and treatment regimens were recorded. Beside whole-brain R2* analyses, regional R2*-values were extracted in putamen, globus pallidum, caudate nucleus, thalamus and red nucleus; hippocampal volumes were also determined. RESULTS: Regional analyses yielded no significant differences between patients and controls, except in those treated with deferiprone that showed lower R2*-values (p<0.05). Whole-brain analyses of R2*-maps revealed strong age-R2* correlations (r2=0.51) in both groups and clusters of significantly increased R2*-values in beta-thalassemia patients in the hippocampal formations and around the Luschka foramina; transfusion treatment was associated with additional R2* increase in dorsal thalami. Hippocampal formation R2*-values did not correlate with hippocampal volume; hippocampal volume did not differ between patients and controls. All regions with increased R2*-values shared a strict anatomical contiguity with choroid plexuses suggesting a blooming effect as the likely cause of R2* increase, in agreement with the available histopathologic literature evidence. CONCLUSION: According to our MRI findings and the available histopathologic literature evidence, concerns about neural tissue iron overload in beta-thalassemia appear to be unjustified.


Assuntos
Encéfalo/diagnóstico por imagem , Sobrecarga de Ferro/diagnóstico por imagem , Ferro/análise , Talassemia beta/diagnóstico por imagem , Adolescente , Adulto , Química Encefálica , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Int J Mol Sci ; 20(21)2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31671722

RESUMO

Methyl-CpG binding protein 2 (MeCP2) is a multi-function factor involved in locus-specific transcriptional modulation and the regulation of genome architecture, e.g., pericentric heterochromatin (PCH) organization. MECP2 mutations are responsible for Rett syndrome (RTT), a devastating postnatal neurodevelopmental disorder, the pathogenetic mechanisms of which are still unknown. MeCP2, together with Alpha-thalassemia/mental retardation syndrome X-linked protein (ATRX), accumulates at chromocenters, which are repressive PCH domains. As with MECP2, mutations in ATRX cause ATR-X syndrome which is associated with severe intellectual disability. We exploited two murine embryonic stem cell lines, in which the expression of MeCP2 or ATRX is abolished. Through immunostaining, chromatin immunoprecipitation and western blot, we show that MeCP2 and ATRX are reciprocally dependent both for their expression and targeting to chromocenters. Moreover, ATRX plays a role in the accumulation of members of the heterochromatin protein 1 (HP1) family at PCH and, as MeCP2, modulates their expression. Furthermore, ATRX and HP1 targeting to chromocenters depends on an RNA component. 3D-DNA fluorescence in situ hybridization (FISH) highlighted, for the first time, a contribution of ATRX in MeCP2-mediated chromocenter clustering during neural differentiation. Overall, we provide a detailed dissection of the functional interplay between MeCP2 and ATRX in higher-order PCH organization in neurons. Our findings suggest molecular defects common to RTT and ATR-X syndrome, including an alteration in PCH.


Assuntos
Diferenciação Celular/fisiologia , Heterocromatina/metabolismo , Proteína 2 de Ligação a Metil-CpG/metabolismo , Neurônios/metabolismo , Proteína Nuclear Ligada ao X/metabolismo , Animais , Diferenciação Celular/genética , Homólogo 5 da Proteína Cromobox , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Modelos Animais de Doenças , Células-Tronco Embrionárias , Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Heterocromatina/química , Heterocromatina/genética , Hibridização in Situ Fluorescente , Deficiência Intelectual/genética , Deficiência Intelectual Ligada ao Cromossomo X/genética , Proteína 2 de Ligação a Metil-CpG/genética , Camundongos , Mutação , Síndrome de Rett/genética , Proteína Nuclear Ligada ao X/química , Proteína Nuclear Ligada ao X/genética , Talassemia alfa/genética
12.
BMC Cardiovasc Disord ; 19(1): 245, 2019 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694552

RESUMO

BACKGROUND: The leading cause of mortality of thalassemia major patients is iron overload cardiomyopathy. Early diagnosis with searching for left ventricular diastolic dysfunction before the systolic dysfunction ensued might yield better prognosis. This study aimed to define the prevalence of the left ventricular diastolic dysfunction (LVDD) in thalassemia major patients with normal left ventricular systolic function and the associated factors. METHODS: Adult thalassemia major patients with normal left ventricular systolic function who were referred for cardiac T2* at Siriraj Hospital - Thailand's largest national tertiary referral center - during the October 2014 to January 2017 study period. Left ventricular diastolic function was defined by mitral valve filling parameters and left atrial volume index using CMR. Patients with moderate to severe valvular heart disease, pericardial disease, or incomplete data were excluded. Baseline characteristics, comorbid diseases, current medication, and laboratory results were recorded and analyzed. RESULTS: One hundred and sixteen patients were included, with a mean age of 27.5 ± 13.5 years, 57.8% were female, and 87.9% were transfusion dependent. Proportions of homozygous beta-thalassemia and beta-thalassemia hemoglobin E were 12.1 and 87.9%, respectively. The baseline hematocrit was 26.3 ± 3.3%. The prevalence of LVDD was 20.7% (95% CI: 13.7-29.2%). Cardiac T2* was abnormal in 7.8% (95% CI: 3.6-14.2%). Multivariate analysis revealed age, body surface area, homozygous beta-thalassemia, splenectomy, heart rate, and diastolic blood pressure to be significantly associated with LVDD. CONCLUSIONS: LVDD already exists from the early stages of the disease before the abnormal heart T2 * is detected. Homozygous beta-thalassemia and splenectomy were strong predictors of LVDD. These data may increase awareness of the disease, especially in the high risk groups.


Assuntos
Imagem Cinética por Ressonância Magnética , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/epidemiologia , Função Ventricular Esquerda , Talassemia beta/epidemiologia , Adolescente , Adulto , Diástole , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Prevalência , Medição de Risco , Fatores de Risco , Sístole , Tailândia/epidemiologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto Jovem , Talassemia beta/diagnóstico
13.
Hemoglobin ; 43(4-5): 283-285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31718331

RESUMO

ß-Thalassemia (ß-thal) is a hereditary and heterogeneous group of disorders caused by mutations on the ß-globin gene that result in the reduced or non production of ß-globin chains. We report a rare ß-globin mutation, IVS-II-848 (C>A) (HBB: c.316-3C>A), which was found in a female Syrian patient. This mutation was associated with the IVS-I-1 (G>A) (HBB: c.92+1G>A) mutation, and the genotype is a compound heterozygote for IVS-I-1(G>A)/IVS-II-848(C>A). This combination was found for the first time in Syria.


Assuntos
Mutação , Globinas beta/genética , Talassemia beta/genética , Família , Feminino , Genótipo , Heterozigoto , Humanos , Síria
14.
Transfus Apher Sci ; 58(6): 102678, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31753776

RESUMO

BACKGROUND: ß-Thalassemia is considered one of the common hemoglobin disorders in the Arabian Peninsula. Red blood cell (RBC) transfusion is a crucial component of the management of transfusion-dependent ß-Thalassemia patients. Patients with Thalassemia Intermedia (TI), also known as non-transfusion dependent ß-thalassemia, have a wide clinical presentation and variable transfusion dependence. Rates of RBC alloimmunization and its risk factors in transfusion-dependent ß-thalassemia patients varied between different reports. Risk of alloimmunization is higher in TI patients. MATERIAL AND METHODS: A literature review on existing reports on alloimmunization rates and risk factors in transfusion dependent and non-transfusion dependent ß-thalassemia in the Eastern Mediterranean region was performed. RESULTS: A total of 17 publications were found. Reported rates of alloimmunization among transfusion-dependent ß-Thalassemia patients ranged between 2.87 and 30 % and between 6.8 and 19.5 % among TI patients. Most centers utilize ABO and RhD matched RBCs. The most common antibodies described are anti-K and anti-E. The risk factors described included age at onset of transfusion, gender, history of splenectomy, duration of transfusion and number of units transfused. Rate of autoantibody formation ranged between 0.1 and 45 %. CONCLUSION: Our review showed variable alloimmunization rates and risk factors in thalassemia patients and scant data on TI patients. The commonest antibodies are anti-K and anti-E. Further studies are required in addressing the rate of alloimmunization, cross-match requirements and role of genotyping in this group of patients. Transfusion support of patients with thalassemia necessitates the availability of blood bank facilities and specialized expertise.


Assuntos
Transfusão de Sangue , Eritrócitos/imunologia , Imunização , Talassemia beta/etiologia , Humanos , Região do Mediterrâneo
15.
J Assist Reprod Genet ; 36(12): 2515-2523, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31758512

RESUMO

PURPOSE: To investigate the validity, accuracy, and clinical outcomes of Karyomapping in preimplantation genetic testing (PGT) for ß-thalassemia combined with human leukocyte antigen (HLA) matching. METHODS: A total of 128 cycles from January 2014 to December 2017 were identified, and 1205 embryos were biopsied. The case group included 88 cycles using Karyomapping for PGT-HLA, compared with 40 cycles using polymerase chain reaction-short tandem repeat (PCR-STR) as the control group. RESULTS: There were significant differences in the HLA matching rate (21.34 vs. 14.37%), the matched transferable embryo rate (9.79 vs. 14.07%), the clinical pregnancy rate (65.08 vs. 41.86%), and the spontaneous miscarriage rate (2.44 vs. 22.22%) between the case and control groups. In the case group, nearly 1/3 (33.37%) of the embryos showed aneuploidy. According to the results of single nucleotide polymorphism (SNP) haplotype analysis, the recombination rates of HBB (hemoglobin subunit beta) and HLA were 11.46% and 5.61% respectively. HLA gene recombination was mostly distributed between HLA-A and HLA-B and the downstream region of HLA-DQB1. In addition, STR analysis could be considered in the case of copy-neutral loss of heterozygosity (LOH) in the region where the HLA gene is located. CONCLUSION: Karyomapping contributes to accurate selection of matched embryos, along with aneuploidy screening. However, STRs assist identification in cases of LOH in the target region.


Assuntos
Antígenos HLA-A/genética , Antígenos HLA-B/genética , Cariotipagem/métodos , Diagnóstico Pré-Implantação , Talassemia beta/diagnóstico , Adulto , Biópsia , Transferência Embrionária , Feminino , Cadeias beta de HLA-DQ/genética , Subunidades de Hemoglobina/genética , Humanos , Perda de Heterozigosidade/genética , Gravidez , Taxa de Gravidez , Talassemia beta/genética , Talassemia beta/patologia
16.
PLoS One ; 14(11): e0225457, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31751397

RESUMO

Thalassemia and hemoglobinopathy is a group of hereditary blood disorder with diverse clinical manifestation inherited by autosomal recessive manner. The Beta thalassemia/Hemoglobin E disease (HbE/ßthal) causes a variable degree of hemolysis and the most severe form of HbE/ßthal disease develop a lifelong transfusion-dependent anemia. Preimplantation genetic testing (PGT) is an established procedure of embryo genetic analysis to avoid the risk of passing on this particular condition from the carrier parents to their offspring. Preimplantation genetic testing for chromosomal aneuploidy (PGT-A) also facilitates the selection of embryos without chromosomal aberration resulting in the successful embryo implantation rate. Herein, we study the clinical outcome of using combined PGT-M and PGT-A in couples at risk of passing on HbE/ßthal disease. The study was performed from January 2016 to December 2017. PGT-M was developed using short tandem repeat linkage analysis around the beta globin gene cluster and direct mutation testing using primer extension-based mini-sequencing. Thereafter, we recruited 15 couples at risk of passing on HbE/ßthal disease who underwent a combined total of 22 IVF cycles. PGT was performed in 106 embryos with a 3.89% allele drop-out rate. Using combined PGT-M and PGT-A methods, 80% of women obtained satisfactory genetic testing results and were able to undergo embryo transfer within the first two cycles. The successful implantation rate was 64.29%. PGT accuracy was evaluated by prenatal and postnatal genetic confirmation and 100% had a genetic status consistent with PGT results. The overall clinical outcome of successful live birth for couples at risk of producing offspring with HbE/ßthal was 53.33%. Conclusively, combined PGT-M and PGT-A is a useful technology to prevent HbE/ßthal disease in the offspring of recessive carriers.


Assuntos
Testes Genéticos/métodos , Hemoglobina E/genética , Diagnóstico Pré-Implantação/métodos , Globinas beta/genética , Talassemia beta/genética , Aneuploidia , Características da Família , Feminino , Fertilização in vitro/estatística & dados numéricos , Humanos , Masculino , Repetições de Microssatélites , Mutação , Gravidez , Estudos Retrospectivos , Análise de Sequência de DNA
17.
Cardiovasc Ultrasound ; 17(1): 24, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684963

RESUMO

BACKGROUND AND OBJECTIVE: Cardiac involvement due to iron overload is the most common cause of morbidity and mortality in patients with thalassemia, and many patients remain asymptomatic until the late stages. Therefore, early detection of heart problems in such patients at subclinical stages can improve the prognosis of these patients. We investigated the role of speckled tracking (SI) and tissue Doppler echocardiography (TDI) in early detection of iron overload in these patients. METHODS: 52 thalassemic patients who were receiving regular blood transfusion with normal global LV function were examined by two- and three-dimensional echocardiography. Cardiac MRI was done and T2* images were considered as the non-invasive gold standard for evaluating cardiac iron deposition. Serum ferritin level was assessed and the relationships between serum ferritin levels and echo finding with cardiac MRI T2* was investigated. RESULTS: No significant relationship was seen between serum ferritin levels and cardiac MRI T2*. Among the echocardiographic findings, septal systolic myocardial velocity (P = 0.002 and r = 0.43) and global strain (GLS) (P = 0.000 and r = 0.60) were significantly associated with T2*. A GLS < 19.5 could predict a T2* level below 20 by 82.14% sensitivity and 86.36% specificity (area under the curve = 0.87; p < 0.0001). CONCLUSION: While serum ferritin level and ejection fraction are not useful candidates, GLS may be used as a valuable marker to screen thalassemia patients for myocardial iron deposition, using a cut off value below - 19.5. This approach may facilitate the cardiac follow up, reduce the costs, and contribute to preventing deterioration of cardiac function in countries with limited availability of cardiac MRI.


Assuntos
Cardiomiopatias/fisiopatologia , Ecocardiografia Doppler/métodos , Ventrículos do Coração/diagnóstico por imagem , Ferro/metabolismo , Imagem Cinética por Ressonância Magnética/métodos , Volume Sistólico/fisiologia , Talassemia/diagnóstico , Doenças Assintomáticas , Biomarcadores/metabolismo , Cardiomiopatias/diagnóstico , Cardiomiopatias/etiologia , Feminino , Ferritinas/sangue , Seguimentos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Miocárdio/metabolismo , Prognóstico , Estudos Retrospectivos , Talassemia/complicações , Talassemia/metabolismo , Função Ventricular Esquerda/fisiologia , Adulto Jovem
18.
Croat Med J ; 60(5): 405-413, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31686454

RESUMO

AIM: To determine whether serum ferritin, liver transaminases, and regularity and type of iron chelation protocol can be used to predict liver iron load as assessed by T2* magnetic resonance imaging (MRI) in patients with beta thalassemia major (TM). METHODS: This cross-sectional study, conducted from March 1, 2014 to March 1, 2015, involved 90 patients with beta TM on regular packed red blood cell transfusion. Liver and cardiac iron load were evaluated with T2* MRI. Compliance with iron-chelating agents, deferoxamine or deferasirox, and regularity of their use, as well as serum ferritin and liver transaminase levels were assessed. RESULTS: Patients with high serum ferritin were 2.068 times (95% confidence interval 1.26-3.37) more likely to have higher liver or cardiac iron load. High serum aspartate aminotransferases and irregular use of iron chelating agents, but not their type, predicted higher cardiac iron load. In a multiple regression model, serum ferritin level was the only significant predictor of liver and myocardial iron load. CONCLUSIONS: Higher serum ferritin strongly predicted the severity of cardiac and liver iron load. Irregular use of chelator drugs was associated with a higher risk of cardiac and liver iron load, regardless of the type of chelating agent.


Assuntos
Ferritinas/sangue , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro , Talassemia beta , Estudos Transversais , Humanos , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/terapia , Fígado/química , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética , Adesão à Medicação/estatística & dados numéricos , Talassemia beta/sangue , Talassemia beta/complicações , Talassemia beta/epidemiologia , Talassemia beta/terapia
19.
Hemoglobin ; 43(4-5): 245-248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687860

RESUMO

The capillary electrophoresis (CE) system allows the quantification of Hb Bart's (γ4) and Hb H (ß4) that is used for screening of Hb H disease. However, Hb Bart's hydrops fetalis and Hb H are not always codetected in patients with Hb H disease. In this study, 35 samples were analyzed for the α0-thalassemia (α0-thal) [- -SEA (Southeast Asian) and - -THAI (Thailand)] deletions and the α+-thal [-α3.7 (rightward) and -α4.2 (leftward)] type deletions using real time-polymerase chain reaction (real time-PCR) with SYBR Green1 and high-resolution melting (HRM) analysis and conventional gap-PCR techniques, respectively. Results showed that 28 of 29 (96.6%) samples with the Hb A2-Hb H phenotype on CE electrophoregrams presented the genotype of - -SEA/-α3.7, while the - -SEA/-α4.2 made up the remainder. The - -SEA/-α3.7 genotype was also found in all six samples (100.0%) with Hb A2-Hb Bart's on CE electrophoregrams. Thus, for genetic counseling, prevention and control programs of Hb Bart's hydrops fetalis and Hb H disease, α-thal genotype analysis is required.


Assuntos
Eletroforese Capilar/métodos , Hemoglobina A2/genética , Hemoglobina H/genética , Hemoglobinas Anormais/genética , Deleção de Sequência , Feminino , Genótipo , Humanos , Hidropisia Fetal/diagnóstico , Gravidez , Diagnóstico Pré-Natal/métodos , Talassemia alfa/diagnóstico , Talassemia alfa/genética
20.
Medicine (Baltimore) ; 98(44): e17612, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689767

RESUMO

RATIONALE: Extramedullary hematopoiesis (EMH) is a rare disease characterized by the formation of hematopoietic elements outside the bone marrow driven by several hematological disease. To the best of our knowledge, EMH is relatively common in patient with beta-thalassemia or hereditary spherocytosis but rarely reported in patients with alpha-thalassemia. Here, we discuss a large intrathoracic EMH (measuring 95 mm × 66 mm) without presenting severe complications in alpha-thalassemia along with literature review. PATIENT CONCERNS: A 55-year-old Chinese female patient with alpha-thalassemia presented with ipsilateral pleural effusion and low hemoglobin level. DIAGNOSIS: Lung cancer was suspected at first and the mass was subjected to CT-guided percutaneous mediastinum biopsy and the pathology confirmed the final diagnosis of extramedullary hematopoiesis. INTERVENTIONS: Blood transfusion, thoracentesis and regular follow up were scheduled rather than surgical interventions or radiotherapy since our patient did not exhibit significant symptoms. OUTCOMES: After 6 months' regular follow up, the patient exhibited no evidence of disease progress. LESSONS: EMH is frequently misdiagnosed and should be differentiated from other masses in thoracic cavity, especially when the underlying hematological disease is discovered. Treatment methods of EMH include surgical resection, hyper-transfusion, hydroxyurea, low-dose radiation or a combination of them.


Assuntos
Hematopoese Extramedular/fisiologia , Derrame Pleural/etiologia , Talassemia alfa/complicações , Transfusão de Sangue , Feminino , Humanos , Pessoa de Meia-Idade , Derrame Pleural/terapia , Toracentese
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