Compound Heterozygosity for Two New Mutations in the β‐Globin Gene [Codon 9 (+ TA) and Polyadenylation Site (AATAAA→AAAAAA)] Leads to Thalassemia Intermedia in a Tunisian Patient

Hemoglobin ◽  
2004 ◽  
Vol 28 (3) ◽  
pp. 243-248 ◽  
Author(s):  
Aurelia Jacquette ◽  
Geneviève Le Roux ◽  
Chantal Lacombe ◽  
Michel Goossens ◽  
Serge Pissard
Keyword(s):  
Globin Gene ◽  
Polyadenylation Site ◽  
Compound Heterozygosity ◽  
Thalassemia Intermedia ◽  
Tunisian Patient ◽  
New Mutations

β-thalassemia intermedia due to compound heterozygosity for two β-globin gene promoter mutations, including a novel TATA box deletion

2007 ◽  
Vol 50 (2) ◽  
pp. 363-366 ◽  
Author(s):  
Raveen K. Basran ◽  
Ulrike M. Reiss ◽  
Hong-yuan Luo ◽  
Russell E. Ware ◽  
David H.K. Chui
Keyword(s):  
Globin Gene ◽  
Gene Promoter ◽  
Tata Box ◽  
Compound Heterozygosity ◽  
Thalassemia Intermedia ◽  
Promoter Mutations

scholarly journals beta-thalassemia intermedia in a Brazilian patient with - 101(C > T) and codon 39 (C > T) mutations

2003 ◽  
Vol 121 (1) ◽  
pp. 28-30
Author(s):  
Sylvia Morais de Sousa ◽  
Letícia Khater ◽  
Luís Antônio Peroni ◽  
Karine Miranda ◽  
Marcelo Jun Murai ◽  
...  
Keyword(s):  
Clinical Course ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Hypochromic Anemia ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Thalassemia Intermedia ◽  
Mean Cell Volume ◽  
Molecular Alterations ◽  
Brazilian Patient

CONTEXT: We verified molecular alterations in a 72-year-old Brazilian male patient with a clinical course of homozygous beta-thalassemia intermedia, who had undergone splenectomy and was surviving without regular blood transfusions. The blood cell count revealed microcytic and hypochromic anemia (hemoglobin = 6.5 g/dl, mean cell volume = 74 fl, mean cell hemoglobin = 24 pg) and hemoglobin electrophoresis showed fetal hemoglobin = 1.3%, hemoglobin A2 = 6.78% and hemoglobin A = 79.4%. OBJECTIVE: To identify mutations in a patient with the symptoms of beta-thalassemia intermedia. DESIGN: Molecular inquiry into the mutations possibly responsible for the clinical picture described. SETTING: The structural molecular biology and genetic engineering center of the Universidade Estadual de Campinas, Campinas, Brazil. PROCEDURES: DNA extraction was performed on the patient's blood samples. The polymerase chain reaction (PCR) was done using five specific primers that amplified exons and the promoter region of the beta globin gene. The samples were sequenced and then analyzed via computer programs. RESULTS: Two mutations that cause the disease were found: -101 (C > T) and codon 39 (C > T). CONCLUSIONS: This case represents the first description of 101 (C > T) mutation in a Brazilian population and it is associated with a benign clinical course.

scholarly journals Beta zero-thalassemia in association with a gamma-globin gene quadruplication

Blood ◽  
1986 ◽  
Vol 68 (6) ◽  
pp. 1394-1397
Author(s):  
KG Yang ◽  
JZ Liu ◽  
F Kutlar ◽  
A Kutlar ◽  
C Altay ◽  
...  
Keyword(s):  
Clinical Condition ◽  
Globin Gene ◽  
Normal Chromosome ◽  
Gene Arrangement ◽  
Beta Thalassemia ◽  
Globin Genes ◽  
Thalassemia Intermedia ◽  
Gamma Globin ◽  
Alpha Globin

We have studied the hematology, hemoglobin composition, and globin gene arrangements in one young Turkish boy with a beta zero-thalassemia homozygosity and in 11 of his relatives. Evidence is presented that the chromosome with the beta zero-thalassemia determinant carries a gamma- globin gene quadruplication, perhaps in a -G gamma-G gamma-G gamma-A gamma-gene arrangement. The eight gamma-globin genes in this patient produced G gamma and A gamma chains in a 95 to 5 ratio, and nearly 99% of the patient's hemoglobin was of the fetal type. The clinical condition resembled that of a thalassemia intermedia. HbF levels in eight beta-thalassemia heterozygotes varied between 0.5 and 4.2% and the percentages of G gamma in this HbF averaged at 87% or 95%; this level is to some extent related to the haplotype of the normal chromosome. All subjects carried four alpha-globin genes; a new BglII polymorphism was observed within the psi alpha-globin gene.

scholarly journals Beta-Thalassemia Intermedia: A Single Thalassemia Center Experience from Northeastern Iraq

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Shaema Salih Amin ◽  
Sana Dlawar Jalal ◽  
Kosar Muhammed Ali ◽  
Ali Ibrahim Mohammed ◽  
Luqman Khalid Rasool ◽  
...  
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Beta Thalassemia ◽  
Abnormal Liver Function Test ◽  
Hybridization Technique ◽  
Genetic Modifiers ◽  
Thalassemia Intermedia ◽  
Female Sex ◽  
Increased Risk ◽  
Thalassemia Mutation

Objective. To determine the molecular characterization and disease-associated complications of beta-thalassemia intermedia (β-TI) patients in Sulaymaniyah province, northeastern Iraq. Methods. A total of 159 β-TI patients from 114 families were enrolled. Detection of β-thalassemia mutations was done by reverse hybridization technique and direct gene sequencing. Also, the clinical and hematological data were collected through an electronic-based medical recording system using a designed comprehensive questionnaire. Results. Nineteen different β-globin gene mutations arranged in 37 various genotypes were determined. The most frequent were IVS-II-I (G>A) (47.2%), followed by IVS-I-6 (T>C) (23.3%) and IVS-I-110 (G>A) (5%). Among disease-related morbidities documented, bone disease amounted to 53% (facial deformity and osteoporosis), followed by endocrinopathies 17.6% (growth retardation and subclinical hypothyroidism), cholelithiasis 13.8%, pulmonary hypertension 11.3%, and abnormal liver function test 7.5%, whereas venous thrombosis, extramedullary hemopoiesis, and leg ulcer were less frequently observed. Age≥35 and female sex were risk factors for cholelithiasis, while age was an independent risk for hypothyroidism and female sex was associated with increased risk for osteoporosis. Mean serum ferritin of ≥1000 μg/L was associated with an increased risk of osteoporosis, whereas chelation therapy was protective for a multitude of other complications. Transfusion, on the other hand, increased the risk of osteoporosis, yet it was protective for cholelithiasis and hypothyroidism. Moreover, splenectomy was protective for cholelithiasis, although it was an independent risk for hypothyroidism. Finally, hydroxyurea was associated with an increased risk of osteoporosis, while it was protective for cholelithiasis. Discussion and Conclusion. β+-thalassemia mutation had contributed to 41.25 of families with a less severe β-thalassemia phenotype in the northeastern part of Iraq, justifying the need to investigate the contribution of genetic modifiers in ameliorating disease severity. In addition, the substantial number of β-TI patients developed disease-related morbidities, which necessitates the need for more appropriate clinical management with earlier intervention.

Mild Hb S-β+-Thalassemia with a Deletion of Five Nucleotides at the Polyadenylation Site of the β-Globin Gene

Hemoglobin ◽  
2003 ◽  
Vol 27 (4) ◽  
pp. 257-260 ◽  
Author(s):  
Philippe Lacan ◽  
Bénédicte Ponceau ◽  
Martine Aubry ◽  
Alain Francina
Keyword(s):  
Globin Gene ◽  
Polyadenylation Site ◽  
Hb S

scholarly journals BETA-GLOBIN GENE MUTATIONS IN TURKISH CHILDREN WITH BETA-THALASSEMIA: RESULTS FROM A SINGLE CENTER STUDY

2013 ◽  
Vol 5 (1) ◽  
pp. e2013055 ◽  
Author(s):  
Ali Fettah ◽  
Cengiz Bayram ◽  
Nese Yarali ◽  
Pamir Isik ◽  
Abdurrahman Kara ◽  
...  
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Thalassemia Intermedia ◽  
Turkish Children ◽  
Tertiary Center

Introduction: The beta thalassemias are common genetic disorders in Turkey and in this retrospective study our aim was to evaluate β-globin chain mutations and the phenotypic severity of β-thalassemia patients followed-up in our hospital, a tertiary center which serves patients from all regions of Turkey. Materials and Methods: 106 pediatric patients were analysed for β-globin gene mutations by using DNA analysis. Patients were classified as having β-thalassemia major or β-thalassemia intermedia based on age at diagnosis, transfusion frequency and lowest hemoglobin concentration in between transfusions. Results: There were 106 patients (52.8% female and 47.2% male) with a mean age of 11.2±5 years (1.6 – 22.3 years). Eighty-four (79.2%) patients had β-thalassemia major, whereas the remaining 22 patients (20.8%) were identified as having β-thalassemia intermedia. Overall, 18 different mutations were detected on 212 alleles. The most frequently encountered mutation was IVS I.110 (G>A) (35.3%), followed by Codon 8 del-AA (10.4%), IVS II.1 (G>A) (8%), IVS I.1 (G>A) (7.5%), Codon 39 (C>T) (7.1%) and Codon 5 (-CT) (6.6%), which made up 79.4% of observed mutations. According to present results, IVS I.110 (G>AA) was the most frequent mutation observed in this study, as in other results from Turkey. Evaluation of β-thalassemia mutations in 106 patients with 212 alleles, revealed the presence of homozygous mutation in 85 patients (80.2%) and compound heterozygous mutation in 21 patients (19.8%). The mutations detected in patients with homozygous mutation were IVS I.110 (G>A) (38.8%), Codon 8 del –AA (11.8%), IVS II.1 (G>A) (8.2%) and IVS I.1 (G>A) (8.2%). Observed mutations in the compound heterozygotes were Codon 39 (C>T)/Codon 41-42 (-CTTT) (14.3%), IVS I.110 (G>A)/Codon 39(C>T) (14.3%), IVS I.110 (G>A)/Codon 44(-C) (14.3%), and IVS II.745 (C>G)/ 5’UTR + 22 (G>A) (9.5%). Conclusion: Our hospital is a tertiary referral center that provides care to patients from all over the country, and thus the distribution of mutations observed in the current study is significant in term of representing that of the country as a whole.

scholarly journals Molecular analysis of beta zero-thalassemia intermedia in Sardinia

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 823-827 ◽  
Author(s):  
R Galanello ◽  
E Dessi ◽  
MA Melis ◽  
M Addis ◽  
MA Sanna ◽  
...  
Keyword(s):  
Nonsense Mutation ◽  
Frameshift Mutation ◽  
Globin Gene ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Thalassemia Intermedia ◽  
Mild Phenotype ◽  
Beta Globin Gene ◽  
Alpha Thalassemia

Abstract In this study we have carried out alpha- and beta-globin gene analysis and defined the beta-globin gene polymorphisms in a group of patients with thalassemia intermedia of Sardinian descent. A group of patients (109) with thalassemia major of the same origin served as control. Characterization of the beta-thalassemia mutation showed either a frameshift mutation at codon 6 or a codon 39 nonsense mutation. We found that homozygotes for the frameshift mutation at codon 6 or compound heterozygotes for this mutation and for the codon 39 nonsense mutation develop thalassemia intermedia more frequently than thalassemia major. The frameshift mutation at codon 6 was associated with haplotype IX that contains the C-T change at position -158 5′ to the G gamma globin gene implicated in high gamma chain production and thus the mild phenotype. In patients' homozygotes for codon 39 nonsense mutation, those with thalassemia intermedia more frequently had the two- gene deletion form of alpha-thalassemia, or functional loss of the alpha 2 gene as compared with those with thalassemia major. In a few siblings with thalassemia major and intermedia, the thalassemia intermedia syndrome correlated with the presence of the -alpha/-alpha genotype. No cause for the mild phenotype was detected in the majority of patients who had not inherited either haplotype IX or alpha- thalassemia.

A novel mutation of −73(A→T) in the CCAAT box of the β-globin gene identified in a patient with the mild β-thalassemia intermedia

2007 ◽  
Vol 86 (9) ◽  
pp. 653-657 ◽  
Author(s):  
Xiao-Wei Chen ◽  
Qiu-Hua Mo ◽  
Qiang Li ◽  
Rong Zeng ◽  
Xiang-Min Xu
Keyword(s):  
Novel Mutation ◽  
Globin Gene ◽  
Thalassemia Intermedia ◽  
Ccaat Box
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