A first case of hemoglobin Castilla [Beta 32(B14) Leu>Arg; HBB: c.98T>G] associated with [IVS-I-1 (G>A); HBB:c.92+1G>A] mutation found in a Syrian betathalassemia patient

Beta thalassemia (β-thal) is one of the most common worldwide inherited hemoglobinopathies. Proper identification and diagnosis of hemoglobin (Hb) variants provide a major challenge. In this report, we describe a 1-year-old boy, presented with the diagnosis of β-TM (beta thalassemia major), has received regular blood transfusions. The molecular analysis revealed the presence of rare Hb Castilla [Beta 32(B14) Leu>Arg; HBB: c.98T>G] variant associated with β0 [IVS-I-1 (G>A); AG^GTTGGT- >AGATTGGT beta0] (HBB:c.92+1G>A) Mutation in beta-globin (β-globin) gene. To our knowledge, this is the first report of Hb Castilla [Beta 32(B14) Leu>Arg] in ExonII of β-globin gene which were found in Syrian male proband. However, we should investigate abnormal hemoglobins in patients with beta thalassemia to determine whether they have involvement with β-thalassemia mutations in the clinical case of the patients or not.

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A Case Report: Infertility Treatment of a Female with Beta-thalassemia Major

Journal of the Bahrain Medical Society ◽

10.26715/jbms.33_2021_2_6 ◽

2021 ◽

Vol 33 (2) ◽

Keyword(s):

Case Report ◽

Medical Condition ◽

Endometrial Thickness ◽

Intrauterine Insemination ◽

Embryo Implantation ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Blood Transfusions ◽

Beta Globin ◽

Beta Thalassemia Major

Beta-thalassemia is caused by a genetically mediated deletion of beta-globin chain of hemoglobin. It is an autosomal recessive disease, which causes a severe medical condition that requires longterm blood transfusions. An impaired hypothalamic-pituitary-ovarian axis mainly causes infertility in such patients. This case report presents a 26-year-old female, a known case of beta-thalassemia major, that received monthly blood transfusions before conceiving. The patient sought consultation for the treatment of primary infertility at Bahrain Defence Force Royal Medical Services (BDF-RMS) Hospital. The patient underwent two trials of intrauterine insemination (IUI). The goal was to build up endometrial thickness by gonadotrophins administration for embryo implantation. To conclude, IUI combined with gonadotrophins for ovarian stimulation has shown success. Keywords: Artificial Insemination, Beta-Thalassemia, Hypogonadism, Infertility, Pregnancy

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Investigation of beta globin gene mutations in Syrian refugee patients with thalassemia major

Turkish Journal of Biochemistry ◽

10.1515/tjb-2018-0492 ◽

2019 ◽

Vol 44 (2) ◽

pp. 126-129

Author(s):

Hatice Çevirici ◽

Can Acıpayam ◽

Ebru Dündar Yenilmez ◽

Fatma Burcu Belen ◽

Esra Pekpak ◽

...

Keyword(s):

Sequence Analysis ◽

Globin Gene ◽

Gene Mutations ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Amplification Refractory Mutation System ◽

Beta Globin ◽

Beta Globin Gene ◽

Beta Thalassemia Major ◽

Mutation System

Abstract Objectives This study, detection of beta globin gene mutations in thalassemia major patients who migrated from Syria to Kahramanmaraş region were planned. Materials and methods The study included 35 Syrian national beta thalassemia major patients. Beta globin gene mutations were detected by ARMS (Amplification Refractory Mutation System) method, RFLP (Restriction Fragment Length Polymorphism) method and DNA sequence analysis. Codon 15, codon 9/10, codon 5 and codon 8 mutations, which we could not detect with other methods in our study, were detected by sequence analysis. Results In beta thalassemia major patients, 16 types of mutations were detected, the most common being IVS-I-110 (n=8). Other mutations are according to frequency order IVS-II-745 (n=3), codon 44 (n=3), codon 15 (n=3), IVS-I-110/IVS-I-1 (n=3), codon 5 (n=2), IVS-I-1 (n=2), codon 8/IVS-II-1 (n=2), codon 44/codon 15 (n=2), IVS-II-1 (n=1), codon 39 (n=1), IVS-I-6/codon 5 (n=1), codon 9/10 (n=1), IVS-I-110/codon 39 (n=1), IVS-I-5/IVS-II-1 (n=1), codon 39/IVS-II-745 (n=1). Conclusions According to the results of our study beta-thalassemia mutations in Syrian immigrant groups show heterogeneity and mutation types of mutation map is similar to Turkey. The conclusion is to prevent families to have a second patient child by genetic counseling.

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Beta-globin gene mutations in children with beta-thalassemia major from Sanliurfa province, Turkey

Turkish Journal of Hematology ◽

10.5152/tjh.2011.86 ◽

2011 ◽

Vol 2011 (4) ◽

pp. 264-268 ◽

Cited By ~ 2

Author(s):

Ali Aycicek ◽

Ahmet Koc ◽

Zeynep Canan Ozdemir ◽

Hasan Bilinc ◽

Abdurrahim Kocyigit ◽

...

Keyword(s):

Globin Gene ◽

Gene Mutations ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Beta Globin ◽

Beta Globin Gene ◽

Beta Thalassemia Major

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Ten Year-Old Male with Hemoglobin Lufkin/Beta-Zero Thalassemia Compound Heterozygote Who Exhibited Beta-Thalassemia Major Characteristics.

Blood ◽

10.1182/blood.v106.11.3815.3815 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3815-3815

Author(s):

Ahna M. Blutreich ◽

Peihong Shu ◽

Jeremy S. Bragdon ◽

Paul J. Kurtin ◽

James D. Hoyer ◽

...

Keyword(s):

High Performance ◽

Globin Gene ◽

Oxygen Affinity ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Target Cells ◽

Beta Globin ◽

First Case ◽

Blood Smear Examination ◽

Thalassemia Mutation

Abstract Hemoglobin Lufkin is a rare and mildly unstable hemoglobin variant with increased oxygen affinity. Since 1977, two cases of hemoglobin Lufkin trait and one hemoglobin Lufkin/hemoglobin S have been described. This report is the first case of hemoglobin Lufkin/beta-zero thalassemia in a 10 year-old Caucasian male of Irish/Italian/German background. The patient presented with jaundice, splenomegaly and thalassemia major facies. On blood smear examination, RBC morphology showed hypochromia, microcytosis, many target cells, some spherocytes and basophilic stippling of RBC’s. On both alkaline hemoglobin (Hb) electrophoresis and isoelectric focusing (IEF) there was an absence of Hb A with a predominant band slightly anodal to the Hb A position. Hb A2 (4.8%)and Hb F (5.3%) were elevated as measured by high performance liquid chromatography. The heat unstable Hb test was abnormal. DNA sequencing of the beta globin gene confirmed a GCC to GAC mutation at codon 29 (gly to asp) consistent with Hb Lufkin. DNA sequence analysis also revealed a beta-zero thalassemia mutation, IVS-1-1, (G to A). The mother’s sample also showed the same beta-thalassemia mutation. Neither hemoglobin Lufkin nor beta-thalassemia were identified in the father; further studies are being done.

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Cytokine Dependent Hematopoietic Cell Linker (CLNK) is Highly Elevated in Blood Transfusion Dependent Beta-Thalassemia Major Patients

10.20944/preprints201904.0054.v1 ◽

2019 ◽

Author(s):

Hussein Kadhem Al-Hakeim ◽

Hawraa Hussein Al-Mayali ◽

Michael Maes

Keyword(s):

Iron Status ◽

Globin Gene ◽

Adaptor Protein ◽

Thalassemia Major ◽

Severe Form ◽

Hematopoietic Cell ◽

Beta Thalassemia ◽

Beta Globin ◽

Beta Thalassemia Major ◽

Globin Chains

Beta-thalassemia major (β-TM) is a severe form of thalassemia caused by mutations in the β-globin gene, resulting in partial or complete deficiency of β-globin chains. This deficiency results in oxidative stress, dyserythropoiesis, and chronic anemia. Cytokine dependent hematopoietic cell linker (CLNK) belongs to the adaptor protein family and has the capacity to interact with multiple signaling proteins thereby modulating signal transduction. The aim of the present study was to examine CLNK in sera of β-TM patients and examine its association with iron overload biomarkers. Sixty β-TM patients, aged 3–12 years old and undergoing blood transfusions, and 30 healthy control children were recruited and CLNK, ferritin and iron status parameters were measured. The results showed a significant increase (p < 0.001) in serum CLNK levels in β-TM patients as compared with normal controls. The increased levels of CLNK were significantly associated with increased ferritin levels. Increased CLNK levels in β-TM may be explained by reciprocal effects between immune signaling and immature erythrocytes, which, release soluble receptors and signaling molecules, including CLNK, in the blood.

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Left Atrial Strain Identifies Increased Atrial Ectopy in Patients with Beta-Thalassemia Major

Diagnostics ◽

10.3390/diagnostics11010001 ◽

2020 ◽

Vol 11 (1) ◽

pp. 1

Author(s):

Maria Vlachou ◽

Vasileios Kamperidis ◽

Efthymia Vlachaki ◽

Georgios Tziatzios ◽

Despoina Pantelidou ◽

...

Keyword(s):

Blood Transfusion ◽

Left Atrial ◽

Systolic Pressure ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Tape Recording ◽

Blood Transfusions ◽

Systolic Strain ◽

Peak Systolic Strain ◽

Beta Thalassemia Major

Patients with beta-thalassemia major (β-ΤΜ) may develop cardiac arrhythmias through a multifactorial mechanism. The current study evaluated the association of cardiac structure and function on echocardiography with atrial ectopic burden on 24-hour tape recording in β-ΤΜ patients. This prospective study included consecutive β-ΤΜ patients. Demographic, laboratory, echocardiographic, cardiac magnetic resonance (CMR) T2* and 24-hour tape recording data were prospectively collected. The patients were classified according to the median value of premature atrial contractions (PACs) on 24-hour tape. In total, 50 β-TM patients (37.6 ± 9.1 years old, 50% male) were divided in 2 groups; PACs ≤ 24/day and > 24/day. Patients with PACs > 24/day were treated with blood transfusion for a longer period of time (39.0 ± 8.6 vs. 32.0 ± 8.9 years, p < 0.007), compared to their counterparts. Older age (OR: 1.121, 95% CI: 1.032–1.217, p = 0.007), longer duration of blood transfusion (OR:1.101, 95% CI:1.019–1.188, p = 0.014), larger LV end-diastolic diameter (OR: 4.522, 95% CI:1.009–20.280, p = 0.049), higher values of LA peak systolic strain (OR: 0.869, 95% CI: 0.783–0.964, p = 0.008), higher MV E/E′ average (OR: 1.407, 95% CI: 1.028–1.926, p = 0.033) and higher right ventricular systolic pressure (OR: 1.147, 95% CI: 1.039–1.266, p = 0.006) were univariably associated with PACs > 24/day. LA peak systolic strain remained significantly associated with PACs > 24/day after adjusting for the duration of blood transfusions or for CMR T2*. The multivariable model including blood transfusion duration and LA peak systolic strain was the most closely associated with PACs > 24/day. Receiver operating characteristic curve analysis identified a left atrial peak systolic strain of 31.5%, as the best cut-off value (83% sensitivity, 68% specificity) for prediction of PACs > 24/day. In β-TM patients, LA peak systolic strain was associated with the atrial arrhythmia burden independently to the duration of blood transfusions and CMR T2*.

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Current Perspective of Beta Thalassemia and Its Treatment Strategies

10.20944/preprints201907.0277.v1 ◽

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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COVID-19 in a Pregnant Patient with Beta-Thalassemia Major: A Case Report

10.22541/au.161899788.81079971/v1 ◽

2021 ◽

Author(s):

Yousef Hailan ◽

Gamal Sayed ◽

mohamed yassin

Keyword(s):

Case Report ◽

Pregnancy Outcome ◽

Pregnant Patient ◽

Threshold Value ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Infection Cycle ◽

First Report ◽

Beta Thalassemia Major ◽

Gestational Week

We report a case of a 35-years-old Lebanese pregnant lady with a background of beta-thalassemia major who was diagnosed with COVID-19 infection (Cycle threshold value 18) during her 23rd gestational week. Unfortunately, the pregnancy outcome was unfavorable. To our knowledge, this is the first report of such a case

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Thyroid Function in Chronically Transfused Children with Beta Thalassemia Major: A Cross-Sectional Hospital Based Study

International Journal of Pediatrics ◽

10.1155/2018/9071213 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 4

Author(s):

Suraj Haridas Upadya ◽

M. S. Rukmini ◽

Sowmya Sundararajan ◽

B. Shantharam Baliga ◽

Nutan Kamath

Keyword(s):

Thyroid Function ◽

Serum Ferritin ◽

Subclinical Hypothyroidism ◽

Thyroid Dysfunction ◽

Genetic Disorder ◽

Thalassemia Major ◽

Beta Thalassemia ◽

P Value ◽

Blood Transfusions ◽

Beta Thalassemia Major

Background. Thalassemia is the most common genetic disorder worldwide. Use of iron chelators has improved survival but endocrine complications have become more frequent. The frequency of hypothyroidism in Beta Thalassemia Major (BTM) children ranges from 6 to 30 %. Thyroid dysfunction mainly occurs by gland infiltration, chronic tissue hypoxia, free radical injury, and organ siderosis. Objectives. (a) To evaluate the thyroid function status in chronically transfused children with BTM, in the first and second decade of life and (b) to study the influence of factors like duration and amount of blood transfusions, serum ferritin level, and iron chelation therapy on thyroid function. Methodology. BTM children, 3 years old and above, on regular blood transfusions with serum ferritin > 1500 mcg/l were included in the study. Thyroid function and ferritin assessment was done using ELISA kits. Autoimmune thyroiditis was ruled out by antithyroid peroxidase and antithyroglobulin antibody testing. Results. A study population of 83 children consisted of 49 boys (59%) and 34 girls (41%). 4.8% of the children had evidence of subclinical hypothyroidism. Among them two belonged to the first decade and the other two to the second decade of life. Mean TSH, FT4, and ferritin values among children with thyroid dysfunction were 6.38 ± 0.83 mIU/ml, 1.08 ± 0.45 ng/dl, and 3983.0±1698.30 ng/ml, respectively. The severity of thyroid dysfunction was statistically significantly associated with higher serum TSH values in children in the second decade of life with a p value = 0.001. No other significant correlation was found between oral chelation, amount and duration of blood transfusion, or serum ferritin levels. Conclusion. Subclinical hypothyroidism was the thyroid dysfunction observed in our study. Regular blood transfusions with adequate chelation may decrease incidence of thyroid dysfunction.

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Hypomethylation of DNA derived from purified human erythroid cells correlates with gene activity of the beta-globin cluster

Blood ◽

10.1182/blood.v66.5.1202.1202 ◽

1985 ◽

Vol 66 (5) ◽

pp. 1202-1207 ◽

Cited By ~ 19

Author(s):

A Oppenheim ◽

Y Katzir ◽

E Fibach ◽

A Goldfarb ◽

E Rachmilewitz

Keyword(s):

Peripheral Blood ◽

Globin Gene ◽

Genetic Regulation ◽

Inverse Correlation ◽

Thalassemia Major ◽

Gene Activity ◽

Beta Thalassemia ◽

Globin Genes ◽

Beta Globin ◽

A Site

Abstract Analysis of methylation at the beta-globin gene cluster was carried out on DNA derived from nucleated RBCs (orthochromatic normoblasts) isolated from peripheral blood of patients with beta-thalassemia major or other congenital hemolytic anemia after splenectomy. A procedure to separate these normoblasts from the other nucleated cells of the peripheral blood was developed, providing us with a convenient source of DNA for investigating parameters related to human erythroid differentiation. Blood samples were obtained from six adult patients who express their gamma-globin genes at different levels. Inverse correlation between methylation and gene activity was consistently observed for five of the eight sites analyzed. A site 3′ to the beta gene was always unmethylated, two sites flanking the epsilon gene were always found to be methylated, and two sites 5′ to the two gamma genes, G gamma and A gamma, were hypomethylated in correlation with gamma gene activity of the individual patients. A site 5′ to the delta gene was unmethylated in normoblasts as well as in WBC. No apparent relation between hypomethylation and gene activity was observed for two additional sites. The results suggest that methylation at specific chromosomal locations participate in genetic regulation of the beta- like globin genes in humans.

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