The Role of the Inherited Disorders of Hemoglobin, the First “Molecular Diseases,” in the Future of Human Genetics

Weatherall, D. J.

doi:10.1146/annurev-genom-091212-153500

Cited by 34 publications

(32 citation statements)

References 110 publications

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“…Our understanding of these beta-hemoglobinopathies at both the clinical and molecular levels has increased greatly in recent decades [3]. However, despite a homogeneous genetic mutation, clinical outcomes and response to therapy vary widely among patients with SCD [4].…”

Section: Introductionmentioning

confidence: 99%

LIN28A Expression Reduces Sickling of Cultured Human Erythrocytes

et al. 2014

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Induction of fetal hemoglobin (HbF) has therapeutic importance for patients with sickle cell disease (SCD) and the beta-thalassemias. It was recently reported that increased expression of LIN28 proteins or decreased expression of its target let-7 miRNAs enhances HbF levels in cultured primary human erythroblasts from adult healthy donors. Here LIN28A effects were studied further using erythrocytes cultured from peripheral blood progenitor cells of pediatric subjects with SCD. Transgenic expression of LIN28A was accomplished by lentiviral transduction in CD34(+) sickle cells cultivated ex vivo in serum-free medium. LIN28A over-expression (LIN28A-OE) increased HbF, reduced beta (sickle)-globin, and strongly suppressed all members of the let-7 family of miRNAs. LIN28A-OE did not affect erythroblast differentiation or prevent enucleation, but it significantly reduced or ameliorated the sickling morphologies of the enucleated erythrocytes.

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Section: Introductionmentioning

confidence: 99%

LIN28A Expression Reduces Sickling of Cultured Human Erythrocytes

et al. 2014

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“…7 Moreover, the diagnostic difficulties in the post-neonatal period are well known, especially those relating to the most prevalent forms of α-thal, with deletions of only one or two genes. This is due to the absence of clinical manifestations and the mild laboratory abnormalities, 3,4 or due to diagnostic failures mainly because of technical ineptitude and low concentrations of Hb H, as is the case of the interaction of α-thal and β-thal. 24 However, in this study, similar to others, 10,20,27,30 cases suggestive of α-thal were more common than were cases of heterozygous Hb S, which is a characteristic of Afro-descendants, hence demonstrating the efficiency of the methods used here.…”

Section: Discussionmentioning

confidence: 99%

“…19,25,31 The possible explanations for this great variability in the frequency of hemoglobinopathies are the wide ethnic diversity of the populations studied and the different diagnostic methodologies used. 3,7,10,20,32 Application of more than one method in the initial screening enhances the specificity and proves to be useful for detecting patients with hemoglobinopathies. The screening methods are easy to perform, inexpensive and reproducible in routine practice in laboratories.…”

Section: Discussionmentioning

confidence: 99%

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Hemoglobinopathies in newborns in the southern region of the Triângulo Mineiro, Brazil. Cross-sectional study

Carlos

Souza

et al. 2015

Sao Paulo Med. J.

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CONTEXT AND OBJECTIVE: Hemoglobinopathies are among the commonest and most widespread genetic disorders worldwide. Their prevalence varies according to ethnic composition and/or geographical region. The aim of this study was to investigate the presence of hemoglobinopathies and their association with ethnicity among 1,004 newborns, to confirm the guideline of the Brazilian National Neonatal Screening Program. DESIGN AND SETTING: Cross-sectional study conducted in a public referral hospital in the Triângulo Mineiro region, Minas Gerais, Brazil. METHODS: Qualitative assessment of hemoglobin was performed through electrophoresis on cellulose acetate: at alkaline pH to identify the hemoglobin (Hb) profile and at acid pH to differentiate Hb S from Hb D and Hb C from Hb E and others that migrate to similar positions at alkaline pH. Neutral pH was used to detect Hb Bart's identified in alpha thalassemia (α-thal). The elution method after electrophoresis was used to quantitatively assess hemoglobins. RESULTS: There was predominance of α-thal, with 105 cases (10.46%), followed by Hb S with 61 cases (6.08%, comprising 46 Hb AS, 2 Hb SS and 13 Hb S/α-thal), 9 cases (0.9%) of Hb AC and 6 cases (0.6%) suggestive of beta thalassemia (β-thal). The frequency of hemoglobinopathies was significantly higher among Afro-descendants. CONCLUSIONS: These findings corroborated of the National Neonatal Screening Program for diagnosing sickle cell disease and Hb C, Hb D, Hb E and β-thal hemoglobinopathies. RESUMO CONTEXTO E OBJETIVO:As hemoglobinopatias estão entre as alterações genéticas mais comuns e mundialmente difundidas, variando conforme a composição étnica e/ou geográfica. Nosso objetivo foi verificar a incidência de hemoglobinopatias por métodos de triagem laboratorial e sua associação com a etnia em 1.004 recém-nascidos. TIPO DE ESTUDO E LOCAL: Estudo transversal; realizado em um hospital público de referência do Triângulo Mineiro, Minas Gerais, Brasil. MÉTODOS: Avaliação qualitativa das hemoglobinas foi realizada por eletroforese em acetato de celulose: em pH alcalino para identificação do perfil hemoglobínico, em pH ácido para diferenciação das Hb S da Hb D e Hb C da Hb E, e outras que migrem em posições semelhantes em pH alcalino e em pH neutro para detecção de Hb Bart's, identificada na talassemia alfa (α-thal); e avaliação quantitativa das hemoglobinas pelo método de eluição após eletroforese. RESULTADOS: Houve predomínio da α-thal, com 105 (10,46%) casos, seguida da Hb S, com 61 casos (6,08% -46 Hb AS, 2 Hb SS e 13 Hb S/α-thal), 9 casos (0,9%) de Hb AC e 6 (0,6%) sugestivos de betatalassemia (β-thal). A incidência de hemoglobinopatias foi significantemente maior em afrodescendentes. CONCLUSÕES: Esses achados reforçam a importância do Programa Nacional de Triagem Neonatal para o diagnóstico das síndromes falciformes e hemoglobinopatias C, D, E e β-thal e robustecem os dados da literatura sobre a necessidade da pesquisa da α-thal em sangue de cordão (não identificada pelo Programa Nacional) e em pacientes com anemia ...

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“…The main reason behind this disease is that a group of ancestral disorders have an impact on the protein inside the RBC called haemoglobin. SCD can easily inherited to the child throughout genetic of sickle haemoglobin (Hb S) either from both parents or from one of them measured as abnormal haemoglobin [1].…”

Section: Introductionmentioning

confidence: 99%

A Framework to Support Ubiquitous Healthcare Monitoring and Diagnostic for Sickle Cell Disease

Khalaf

Hussain

Al‐Jumeily

et al. 2015

Intelligent Computing Theories and Methodologies

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Abstract. Recent technology advances based on smart devices have improved the medical facilities and become increasingly popular in association with realtime health monitoring and remote/personals health-care. Healthcare organisations are still required to pay more attention for some improvements in terms of cost-effectiveness and maintaining efficiency, and avoid patients to take admission at hospital. Sickle cell disease (SCD) is one of the most challenges chronic obtrusive disease that facing healthcare, affects a large numbers of people from early childhood. Currently, the vast majority of hospitals and healthcare sectors are using manual approach that depends completely on patient input, which can be slowly analysed, time consuming and stressful. This work proposes an alert system that could send instant information to the doctors once detects serious condition from the collected data of the patient. In addition, this work offers a system that can analyse datasets automatically in order to reduce error rate. A machine-learning algorithm was applied to perform the classification process. Two experiments were conducted to classify SCD patients from normal patients using machine learning algorithm in which 99% classification accuracy was achieved using the Instance-based learning algorithm.

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The Role of the Inherited Disorders of Hemoglobin, the First “Molecular Diseases,” in the Future of Human Genetics

Cited by 34 publications

References 110 publications

LIN28A Expression Reduces Sickling of Cultured Human Erythrocytes

LIN28A Expression Reduces Sickling of Cultured Human Erythrocytes

Hemoglobinopathies in newborns in the southern region of the Triângulo Mineiro, Brazil. Cross-sectional study

A Framework to Support Ubiquitous Healthcare Monitoring and Diagnostic for Sickle Cell Disease

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