scholarly journals Thalassemia intermedia phenotype resulting from rare combination of c.46delT [Codon15 (-T)] mutation of beta globin gene and HPFH3

2017 ◽  
Vol 5 (7) ◽  
pp. 1107-1110 ◽  
Author(s):  
Anjali J. Kelkar ◽  
Anu Moses
Keyword(s):  
Globin Gene ◽  
Beta Globin ◽  
Thalassemia Intermedia ◽  
Beta Globin Gene ◽  
Rare Combination

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.

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 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

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.

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 Mutation in thalassemia syndrome and clinical manifestation

2020 ◽  
Vol 6 (2) ◽  
pp. e29-e29
Author(s):  
Ahmad Tamaddoni ◽  
Leila Gharehdaghly ◽  
Mohammad Bahadoram
Keyword(s):  
Blood Transfusion ◽  
Molecular Basis ◽  
Globin Gene ◽  
Clinical Severity ◽  
Clinical Aspects ◽  
Beta Globin ◽  
Thalassemia Intermedia ◽  
Dot Blot ◽  
Mazandaran Province ◽  
Beta Globin Gene

Introduction: Thalassemia intermedia is a term used to define a group of patients with β thalassemia in whom the clinical severity of the disease is somewhere between the mild symptoms of the β thalassemia trait and the severe manifestations of β thalassemia major. Thalassemia intermedia shows considerable heterogeneity in phenotype and molecular basis. Objectives: The aim of this study was to identify the common mutations of beta globin gene and the relationship between genotypes and phenotypes in thalassemia intermedia patients in Mazandaran province, in the north of Iran. Patients and Methods: Fifty unrelated thalassemia intermedia patients, based on clinical and hematological characteristics including age of diagnosis, age of first blood transfusion, history of blood transfusion, mean corpuscular volume (MCV), mean cell hemoglobin (MCH), hemoglobin values, and liver and spleen status were selected. DNA of peripheral blood was extracted and common mutations in beta globin gene were analyzed by reverse dot blot (RDB) method. Results: Our study showed that 30 patients (60%) had blood transfusion. There was no obvious hepatomegaly in any of the subjects, however 40 patients (80%) showed splenomegaly among which 34 cases (68%) underwent splenectomy. Mutations analysis indicated that HBB:c.315+1G>A [IVS II-1 (G>A)] mutation was the dominant mutation and has been widely associated with the phenotypic manifestations of thalassemia intermedia patients. Conclusion: It is important to comprehend the molecular basis of thalassemia intermedia and the association between genotype and phenotype in different ethnic groups. Therefore a careful evaluation of genetic, molecular, hematological and clinical aspects is necessary to differentiate thalassemia intermedia in patients at presentation.

scholarly journals Molecular characterization of a beta zero-thalassemia resulting from a 1.4 kilobase deletion

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 636-641 ◽  
Author(s):  
R Anand ◽  
CD Boehm ◽  
HH Jr Kazazian ◽  
EF Vanin
Keyword(s):  
Transcriptional Start Site ◽  
Globin Gene ◽  
Event Analysis ◽  
Beta Globin ◽  
Base Pairs ◽  
Dna Polymerase Alpha ◽  
Beta Globin Gene ◽  
American Black ◽  
The Individual

Abstract We report the characterization of a beta zero-thalassemia in an American Black with unusually high HbA2 and HbF levels. Genomic southern analysis indicated that the individual was heterozygous for a deletion that began within the second intervening sequence of the beta- globin gene and extended approximately 1.4 kb in the 5′ direction. A clone spanning the breakpoint on the abnormal chromosome was isolated and further mapped, and the deletion joint was sequenced. Comparison of the normal beta-globin gene and its 5′ flanking region with the deletion joint sequence indicated that the 5′ breakpoint for this deletion was 484 base pairs (bp) 5′ to the transcriptional start site for the beta-globin gene and the 3′ breakpoint was 908 bp into the beta- globin gene; the deletion removed a total of 1,393 bp. Comparison of the normal 5′ and 3′ breakpoint sequences indicated that this deletion was the result of a “clean” nonhomologous breakage and reunion event; ie, no spurious bases were added during the recombinational event. Analysis of the breakpoints of this deletion together with the breakpoints of two other small deletions involving the beta-globin gene suggests that the breakpoints may occur at DNA polymerase alpha pause sites.

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