scholarly journals A novel single gene deletion (-αMAL3.5) giving rise to silent α thalassemia carrier removing the entire HBA2 gene observed in two Chinese patients with Hb H disease: case report of two probands

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Faidatul Syazlin Abdul Hamid ◽  
Rahimah Ahmad ◽  
Mohamed Saleem ◽  
Nur Aisyah Aziz ◽  
Syahira Lazira Omar ◽  
...  
Keyword(s):  
Dna Analysis ◽  
Single Gene ◽  
Globin Gene ◽  
Clinical Findings ◽  
Chinese Patients ◽  
Hematological Indices ◽  
Disease Case ◽  
Pcr Multiplex ◽  
Hb H Disease ◽  
Pcr Method

<p>We report a novel deletion at the <em>HBA2</em> presented with Hb H disease in two Malaysian- Chinese patients. The two unrelated probands were diagnosed with Hb H disease in a primary hematological screening for thalassemia. Results from routine molecular analysis with gap-polymerase chain reaction (PCR) method revealed a genotype asynchrony with the observed clinical presentation. Subsequent DNA analysis using a battery of molecular methods such as gap-PCR, multiplex ligation dependent probe amplification, DNA sequencing, confirmed the presence of a novel deletion in both the index cases removing the entire α2 globin gene. We have designated the deletion as (‒α<sup>MAL3.5</sup>). Hematological indices and clinical findings suggest that the deletion has an α<sup>+</sup> phenotype. The molecular process of this deletion is the result from misalignment and unequal crossover event between the duplicated homologous Y-boxes within the α globin gene cluster. Uncharacterized deletions, single nucleotide polymorphism and other nucleotide indels at the primer binding sites may impede the optimum condition for its annealing and extension and therefore may invalidate the gap-PCR obscuring the real genotype.</p><p> </p><p>我们报告了两例马来西亚华裔患者中随HbH病表现出的一种HBA2的新型缺失。 这两例不相关的先证者在地中海贫血的初步血液筛查中被诊断出患有HbH病。 采用跨越断裂点聚合酶链反应（PCR）方法进行常规分子分析的结果显示出一种与观察到的临床表现不一致的基因型。 后续采用一系列分子方法（如跨越断裂点PCR、多重连接探针扩增、DNA测序）进行的DNA分析证实了这两个指示病例中的新型缺失的存在消除了整个α2珠蛋白基因。 我们将该缺失命名为（-αMAL3.5）。 血液学指标和临床结果提示该缺失具有α+表型。 这种缺失的分子过程是α珠蛋白基因簇内部重复的同源Y-盒之间之间错配和不等交换事件的结果。 未表征的缺失、单核苷酸多态性和其它核苷酸插入/缺失的引物结合位点可能阻碍其退火和延伸的最佳条件，因此可能使跨越断裂点PCR无效，模糊了真实的基因型。</p>

scholarly journals Prolonged Pyrexia: Kikuchi-Fujimoto Disease in a Patient With Hb H-Constant Spring Thalassemia

2020 ◽  
Vol 13 ◽  
pp. 117954762093642
Author(s):  
Ganesh Kasinathan
Keyword(s):  
Dna Analysis ◽  
Complete Blood Count ◽  
Globin Gene ◽  
Oral Prednisolone ◽  
Lymph Node Biopsy ◽  
Whole Body ◽  
Gene Deletions ◽  
Prolonged Fever ◽  
Alpha Globin ◽  
Hb H Disease

Introduction: Haemoglobin H (Hb H) disease is an alpha thalassemia characterised by either 3 alpha-globin gene deletions (deletional type) or 2 alpha-globin gene deletions with 1-point mutation (nondeletional type). Haemoglobin H-Constant Spring thalassemia is the most common Hb H disease in Asia. Kikuchi-Fujimoto disease (KFD) is an important cause of prolonged fever in thalassemia and is often self-limiting. Case Presentation: A 30-year-old women of Malay ethnicity presented to the thalassemia unit with a month history of prolonged fever, headache, and painful enlarged neck lymph nodes. She is known to have Hb H-Constant Spring thalassemia, in which she is on 3-monthly blood transfusion. Physical examination revealed persistent pyrexia of 38°C. She had multiple tender bilateral cervical lymphadenopathies with the largest measuring 4 × 4 cm. The complete blood count revealed hypochromic microcytic anaemia with leucopenia and a normal platelet count. She had hyperferritinemia of 3500 ng/mL. The DNA analysis of alpha-globin gene showed heterozygosity for alpha zero thalassemia South East Asian deletion with termination codon mutation (TAA-CAA) which was consistent with Hb H-Constant Spring thalassemia. Numerous investigations for her prolonged fever including cultures did not yield any positive results. Whole-body computed tomography (CT) imaging showed diffuse lymphadenopathies and hepatosplenomegaly. Finally, a left cervical lymph node biopsy was performed which was consistent with KFD. She was treated with oral prednisolone which was gradually tapered based on response. Currently, she is asymptomatic and is in complete remission. Conclusion: Kikuchi-Fujimoto disease should be considered as a cause for prolonged pyrexia in a patient with thalassemia. An early diagnosis of KFD would avoid an unnecessary battery of investigations. This case highlights the importance of clinicopathological correlation in managing patients with thalassemia as these patients often have other associated morbidities.

Genetic screening of newborns for sickle cell disease: correlation of DNA analysis with hemoglobin electrophoresis

1991 ◽  
Vol 37 (3) ◽  
pp. 454-458 ◽  
Author(s):  
KrIsten J Skogerboe ◽  
Sheyla F West ◽  
Magdalena D Murillo ◽  
Michael W Glass ◽  
Santosh Shaunak ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Genetic Screening ◽  
Dna Analysis ◽  
Globin Gene ◽  
Pcr Analysis ◽  
Beta Globin ◽  
Cell Disease ◽  
Pcr Method ◽  
Few Data

Abstract Although DNA analysis based on the polymerase chain reaction (PCR) offers potential advantages for screening newborns for sickle cell disease, few data are available concerning the reliability of PCR-based tests for such screening. We describe a protocol for detecting the A, S, and C alleles of the beta-globin gene in dried blood from phenylketonuria screening cards. This method is based on PCR and detection with allele-specific oligonucleotide probes. Results of a blind comparison of PCR analysis of the dried blood with hemoglobin electrophoresis of whole-blood samples agreed for 80 of 81 samples. The single discrepancy is probably not attributable to a failure of the PCR method, but rather to limitations of the electrophoresis method. The PCR method should be a highly accurate means of detecting beta-globin alleles in routine genetic screening with dried blood already collected for (e.g.) phenylketonuria screening.

Status research Thalassemia carier among children of ethnic Tay, Dao in Tuyen Quang province

2021 ◽  
Vol 05 (03) ◽  
pp. 102-109
Author(s):  
Thi Thu Giang Do ◽  
◽  
Quang Thanh Pham ◽  
Phuong Thuy Ho
Keyword(s):  
Ethnic Minority ◽  
Dna Analysis ◽  
Single Gene ◽  
Hematological Parameters ◽  
Globin Gene ◽  
Gene Mutations ◽  
Screening Tests ◽  
Minority Children ◽  
Alpha Globin ◽  
Ethnic Minority Children

Objectives: To determine the prevalence of thalassemia carrier, genotype and hematological parameters among children bearing the thalassemia gene in Tuyen Quang. Methodology: A descriptive study was conducted from January to March 2017. 505 ethnic minority children in 6 districts and Tuyen Quang City, Tuyen Quang province were registered voluntarily by the family in the study. MCV index <80fL combined with the DCIP test were used for screening thalassemia and HbE. Hemoglobin electrophoresis and DNA analysis of mutations in the globin alpha gene was performed for all cases positive with screening tests. Results: The prevalence of thalassemia common for ethnic minority children in Tuyen Quang was 28,1%. Four types of single-gene mutations in the alpha globin gene were identified, following types --SEA, -α3.7; -αCS; -α4.2. Conclusion: The general prevalence of thalassemia gene among the Tay and Dao children in Tuyen Quang is 28.1%. Six phenotypic groups carrying thalassemia gene were detected with 10 mutant genotypes. Mutation - SEA accounts for the highest proportion of single allele mutations (72.09%). Keywords: Thalassemia carrier, children, ethnic Tay, ethnic Dao, Tuyen Quang

Significance of genetic counseling and prenatal diagnosis on α2 codon 30 (-GAG) (HBA2: c.91_93delGAG) mutation

2019 ◽  
Author(s):  
Zhiyang Guan ◽  
Zeyan Zhong ◽  
Hailin He ◽  
Dan Chen ◽  
Guoxing Zhong ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Prenatal Diagnosis ◽  
Dna Analysis ◽  
Globin Gene ◽  
Gene Mutations ◽  
Severe Form ◽  
Clinical Severity ◽  
Globin Genes ◽  
Significant Difference ◽  
Hb H Disease

Abstract Background : Non-deletional hemoglobin (Hb) H disease is the severest form of α- thalassemia ( thal ) compatible with post-natal life, which is caused by the interaction of an α-globin gene mutation with α 0 -thal. Therefore, it is important to identify rare α-globin gene mutations for the prevention of severe form of non-deletional Hb H disease . Methods: In all, 61,796 samples were characterized at our center. Common α- and β- thalassemia mutations were detected by routine DNA analysis (gap-PCR and PCR-RDB ). The DNA sequencing of α-globin genes was performed to identify the unknown mutation. Statistical analyses were conducted using SPSS 19.0 statistical software. Results: Of the 61,796 samples, eight were identified as α2 codon 30 (-GAG) ( HBA2 : c.91_93delGAG) mutation s, and of these, four had coinheritance with - - SEA deletion Patients with the heterozygous α2 codon 30 (-GAG) ( HBA2 : c.91_93delGAG) mutation had significantly lower levels of MCV and MCH than healthy individuals ( p < 0.01), and coinheritance with - - SEA deletion aggravated the α-thal phenotype , associated with severe Hb H disease . Moreover, a significant difference in the clinical severity was found in the Hb H disease patients with the same genotype.Conclusions: This finding is of great significance for clinicians to provide accurate genetic counseling , particularly prenatal diagnosis and establish a rigorous diagnostic procedure .

scholarly journals A Clinical-Based Diagnostic Approach to Cerebellar Atrophy in Children

2021 ◽  
Vol 11 (5) ◽  
pp. 2333
Author(s):  
Claudia Ciaccio ◽  
Chiara Pantaleoni ◽  
Franco Taroni ◽  
Daniela Di Bella ◽  
Stefania Magri ◽  
...  
Keyword(s):  
Muscle Biopsy ◽  
Single Gene ◽  
Brain Mri ◽  
Genetic Defect ◽  
Cerebellar Atrophy ◽  
Chain Complex ◽  
Clinical Findings ◽  
Diagnostic Workup ◽  
Diagnostic Approach ◽  
Disease Definition

Background: Cerebellar atrophy is a neuroradiological definition that categorizes conditions heterogeneous for clinical findings, disease course, and genetic defect. Most of the papers proposing a diagnostic workup for pediatric ataxias are based on neuroradiology or on the literature and experimental knowledge, with a poor participation of clinics in the process of disease definition. Our study aims to offer a different perspective on the way we approach cerebellar atrophy in developmental age, building a clinical-based diagnostic workup to guide molecular diagnosis. Methods: we recruited 52 patients with pediatric-onset cerebellar atrophy and definite disease categorization. Children underwent brain MRI, neurophysiological exams, metabolic investigations, and muscle biopsy with respiratory chain complex study. Single-gene sequencing, next-generation sequencing NGS panels, whole-exome sequencing (WES), and disease-specific techniques have been used to reach genetic confirmation. Results: Brain MRI is the main method of diagnosis, followed by tests on muscle biopsy and peripheral nervous system study. Other exams (e.g., metabolic investigations or evoked potentials) may be useful to narrow the list of diagnostic possibilities. Conclusions: We propose a diagnostic approach to cerebellar atrophy in children based on clinical findings, and support the evidence that a precise phenotypic definition may lead to the formulation of a definite diagnosis or otherwise guide the back phenotyping process derived from large molecular data.

Pathophysiology and therapy for haemoglobinopathies; Part II: thalassaemias

2006 ◽  
Vol 8 (10) ◽  
pp. 1-26 ◽  
Author(s):  
Fabrizia Urbinati ◽  
Catherine Madigan ◽  
Punam Malik
Keyword(s):  
Single Gene ◽  
Globin Gene ◽  
Marrow Transplant ◽  
World Population ◽  
Symptomatic Therapy ◽  
Globin Genes ◽  
Cell Disease ◽  
Critical Function ◽  
Single Gene Disorders ◽  
Clinical Syndromes

Thalassaemias result from mutations of the globin genes that cause reduced or absent haemoglobin production and thus interfere with the critical function of oxygen delivery. They represent the most common single-gene disorders, with 4.83% of the world population carrying globin gene variants. Reduced or absent α-globin (α-thalassaemia) or β-globin (β-thalassaemia) leads to anaemia and multifaceted clinical syndromes. In this second of two reviews on the pathophysiology of haemoglobinopathies, we describe the clinical features, pathophysiology and molecular basis of α- and β-thalassaemias. We then discuss current targeted therapies, including the new oral iron chelators, which, along with chronic transfusions, constitute the mainstay of symptomatic therapy for the majority of patients. Finally, we describe potentially curative therapies, such as bone marrow transplant, and discuss some of the outstanding research studies and questions, including the upcoming field of gene therapy for β-thalassaemia. An accompanying article on haemoglobinopathies (Part I) focuses on sickle cell disease.

scholarly journals The polyadenylation site mutation in the alpha-globin gene cluster

Blood ◽  
1988 ◽  
Vol 71 (2) ◽  
pp. 313-319 ◽  
Author(s):  
SL Thein ◽  
RB Wallace ◽  
L Pressley ◽  
JB Clegg ◽  
DJ Weatherall ◽  
...  
Keyword(s):  
Middle Eastern ◽  
Globin Gene ◽  
Saudi Arabian ◽  
Polyadenylation Signal ◽  
Enzyme Analysis ◽  
Restriction Enzyme Analysis ◽  
Site Mutation ◽  
Mediterranean Populations ◽  
Alpha Globin ◽  
Hb H Disease

In a previous study, we described a form of nondeletion alpha- thalassemia (alpha T Saudi alpha) found in subjects of Saudi Arabian origin. In the current study, using synthetic oligoprobe hybridization and restriction enzyme analysis, we have demonstrated that the molecular basis of alpha T Saudi alpha is due solely to a single base mutation (AATAAA----AATAAG) in the polyadenylation signal of the alpha 2 gene and that the frameshift mutation in codon 14 of the linked alpha 1 gene is the result of a cloning artefact. The alpha 2 polyadenylation signal mutation occurs in other Middle Eastern and the Mediterranean populations and is responsible for the clinical phenotype of Hb H disease in some Saudi Arabian individuals with five alpha genes (alpha T Saudi alpha/(alpha alpha alpha)T Saudi). Evidence suggests that the (alpha alpha alpha)T Saudi haplotype has arisen as a result of a recombination between two misaligned chromosomes bearing the alpha T Saudi alpha defect.

scholarly journals Development of multiplex real-time RT-PCR assay for the detection of SARS-CoV-2

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250942
Author(s):  
Huseyin Tombuloglu ◽  
Hussein Sabit ◽  
Ebtesam Al-Suhaimi ◽  
Reem Al Jindan ◽  
Khaled R. Alkharsah
Keyword(s):  
Real Time ◽  
Single Gene ◽  
False Negative ◽  
Diagnostic System ◽  
Virus Detection ◽  
Current Method ◽  
Pcr Method ◽  
Polymerase Chain ◽  
Positive Results ◽  
Good Agreement

The outbreak of the new human coronavirus SARS-CoV-2 (also known as 2019-nCoV) continues to increase globally. The real-time reverse transcription polymerase chain reaction (rRT-PCR) is the most used technique in virus detection. However, possible false-negative and false-positive results produce misleading consequences, making it necessary to improve existing methods. Here, we developed a multiplex rRT-PCR diagnostic method, which targets two viral genes (RdRP and E) and one human gene (RP) simultaneously. The reaction was tested by using pseudoviral RNA and human target mRNA sequences as a template. Also, the protocol was validated by using 14 clinical SARS-CoV-2 positive samples. The results are in good agreement with the CDC authorized Cepheid`s Xpert® Xpress SARS-CoV-2 diagnostic system (100%). Unlike single gene targeting strategies, the current method provides the amplification of two viral regions in the same PCR reaction. Therefore, an accurate SARS-CoV-2 diagnostic assay was provided, which allows testing of 91 samples in 96-well plates in per run. Thanks to this strategy, fast, reliable, and easy-to-use rRT-PCR method is obtained to diagnose SARS-CoV-2.

scholarly journals Current Perspective of Beta Thalassemia and Its Treatment Strategies

2019 ◽  
Author(s):  
Shaukat Ali ◽  
Shumaila Mumtaz ◽  
Hafiz Abdullah Shakir ◽  
Hafiz Muhammad Tahir ◽  
Tafail Akbar Mughal
Keyword(s):  
Genetic Testing ◽  
Blood Transfusion ◽  
Dna Analysis ◽  
Complete Blood Count ◽  
Globin Gene ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Hematopoietic Stem ◽  
Thalassemia Minor

Thalassemia is genetic blood disease cause by absence or decrease of one or more of the globin chain synthesis. Beta thalassemia is characterized by one or more mutations in beta globin gene. Absence or reduced amount the of beta globin chains cause ineffective erythropoiesis which leads to anemia. Beta thalassemia has been further divided into three main forms: Thalassemia minor/silent carrier, major and intermedia. More severe form is thalassemia major in which patients depend upon blood transfusion for survival and high level of iron occur as a consequence of consistent blood transfusion. Over loaded iron invokes the synthesis of reactive oxygen species that are toxic in redundancy and triggering the impairment to vascular, endocrine and hepatic system. Thalassemia can be diagnosed and detected through various laboratory tests such as blood smear, prenatal testing (genetic testing of amniotic fluid), DNA analysis (genetic testing) and complete blood count. Treatment of thalassemia intermedia is symptomatic but it can also be managed by splenectomy and folic supplementation. While thalassemia major can be treated by transplantation of bone marrow, regular transfusion of blood and iron chelation treatment, stimulation of fetal hemoglobin production, hematopoietic stem cell transplantation and gene therapy.

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