Compound heterozygosity of a silent beta‐thalassemia mutation at the 3′‐untranslated region ( HBB : c.*132 C>T) and beta‐zero thalassemia results in thalassemia intermedia

2020 ◽  
Vol 67 (4) ◽  
Author(s):  
Adivitch Sripusanapan ◽  
Arunee Phusua ◽  
Kanda Fanhchaksai ◽  
Pimlak Charoenkwan
Keyword(s):  
Untranslated Region ◽  
Beta Thalassemia ◽  
Compound Heterozygosity ◽  
Thalassemia Intermedia ◽  
Thalassemia Mutation

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.

scholarly journals Molecular characterization of beta-thalassemia intermedia in patients of Italian descent and identification of three novel beta-thalassemia mutations

Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1342-1347 ◽  
Author(s):  
S Murru ◽  
G Loudianos ◽  
M Deiana ◽  
C Camaschella ◽  
GV Sciarratta ◽  
...  
Keyword(s):  
Blot Analysis ◽  
Globin Gene ◽  
Beta Thalassemia ◽  
Italian Population ◽  
Beta Globin ◽  
Thalassemia Intermedia ◽  
Dot Blot ◽  
Beta Globin Gene ◽  
Dot Blot Analysis ◽  
Thalassemia Mutation

Abstract In this study, we have defined by dot-blot analysis with allelic specific oligonucleotide probes or direct sequencing on amplified DNA the beta-thalassemia mutations in a large group of patients (23) of Italian descent with thalassemia intermedia. These patients had one parent with either the silent beta-thalassemia carrier phenotype or borderline-normal hemoglobin A2 (HbA2) levels (2.5% to 3.5%). Nearly all were genetic compounds for a severe beta-thalassemia mutation and a beta-thalassemia mutation associated with high residual output of beta- globin chains (beta + intervening sequence [IVS]-I-nt6, beta -87, beta - 101), indicating that inheritance of a mild beta-thalassemia allele, even in a single dose, is the most common molecular mechanism producing thalassemia intermedia in the Italian population. In three cases, in whom we failed to define by dot-blot analysis the mutations, we sequenced the beta + globin gene and found three novel beta-thalassemia mutations, which are certainly very rare because they have been hitherto detected solely in a single patient. These mutations consist of: (1) a T-A substitution at position 2 of IVS-I, in a patient compound heterozygote for this mutation and the -87 promoter mutation; (2) a G-C substitution at position 844 of IVS-II, in a patient heterozygous for this mutation who showed normal sequences at the in trans beta-globin gene (The reason for the presence of clinical manifestations in a beta-thalassemia heterozygote has not been defined.); and (3) a deletion of one nucleotide (-T) at codon 126, resulting in a frameshift and readthrough of the 5′ untranslated region and most likely producing an elongated Hb molecule of 156 amino acid residues, in a patient heterozygous for this mutation with normal beta- globin gene sequences at the other locus.

scholarly journals Molecular characterization of beta-thalassemia intermedia in patients of Italian descent and identification of three novel beta-thalassemia mutations

Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1342-1347 ◽  
Author(s):  
S Murru ◽  
G Loudianos ◽  
M Deiana ◽  
C Camaschella ◽  
GV Sciarratta ◽  
...  
Keyword(s):  
Blot Analysis ◽  
Globin Gene ◽  
Beta Thalassemia ◽  
Italian Population ◽  
Beta Globin ◽  
Thalassemia Intermedia ◽  
Dot Blot ◽  
Beta Globin Gene ◽  
Dot Blot Analysis ◽  
Thalassemia Mutation

In this study, we have defined by dot-blot analysis with allelic specific oligonucleotide probes or direct sequencing on amplified DNA the beta-thalassemia mutations in a large group of patients (23) of Italian descent with thalassemia intermedia. These patients had one parent with either the silent beta-thalassemia carrier phenotype or borderline-normal hemoglobin A2 (HbA2) levels (2.5% to 3.5%). Nearly all were genetic compounds for a severe beta-thalassemia mutation and a beta-thalassemia mutation associated with high residual output of beta- globin chains (beta + intervening sequence [IVS]-I-nt6, beta -87, beta - 101), indicating that inheritance of a mild beta-thalassemia allele, even in a single dose, is the most common molecular mechanism producing thalassemia intermedia in the Italian population. In three cases, in whom we failed to define by dot-blot analysis the mutations, we sequenced the beta + globin gene and found three novel beta-thalassemia mutations, which are certainly very rare because they have been hitherto detected solely in a single patient. These mutations consist of: (1) a T-A substitution at position 2 of IVS-I, in a patient compound heterozygote for this mutation and the -87 promoter mutation; (2) a G-C substitution at position 844 of IVS-II, in a patient heterozygous for this mutation who showed normal sequences at the in trans beta-globin gene (The reason for the presence of clinical manifestations in a beta-thalassemia heterozygote has not been defined.); and (3) a deletion of one nucleotide (-T) at codon 126, resulting in a frameshift and readthrough of the 5′ untranslated region and most likely producing an elongated Hb molecule of 156 amino acid residues, in a patient heterozygous for this mutation with normal beta- globin gene sequences at the other locus.

scholarly journals PB2403 ROLE OF HYDROXYUREA IN BETA THALASSEMIA INTERMEDIA

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 1068
Author(s):  
A. Mahesar ◽  
M. Mazari
Keyword(s):  
Beta Thalassemia ◽  
Thalassemia Intermedia

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-thalassemia Intermedia From Two Japanese Families

1977 ◽  
Vol 16 (4) ◽  
pp. 375-382
Author(s):  
Jun SASAKI ◽  
Takashi IMAMURA ◽  
Kiyohide NUNOI ◽  
Katsunori SHIBATA ◽  
Kotaro YAMAOKA ◽  
...  
Keyword(s):  
Beta Thalassemia ◽  
Thalassemia Intermedia

Spinal Cord Compression in Homozygous Beta-Thalassemia Intermedia

1994 ◽  
Vol 20 (3) ◽  
pp. 186-189 ◽  
Author(s):  
E. Cardia ◽  
S. Toscano ◽  
G. La Rosa ◽  
C. Zaccone ◽  
D. d’Avella ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Cord Compression ◽  
Beta Thalassemia ◽  
Thalassemia Intermedia
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