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![Sequencing for the detection of rare mutations in the beta globin gene in the region from Promoter to IVS2. 1. Mother: Heterozygous for c.46delT [Cod15 (-T)], 2. Patient: Homozygous pattern for c.46delT [Cod15 (-T)], 3. Father: Normal.](publication/318133760/figure/fig3/AS:518707941654528@1500681018210/Sequencing-for-the-detection-of-rare-mutations-in-the-beta-globin-gene-in-the-region-from.png)
Sequencing for the detection of rare mutations in the beta globin gene in the region from Promoter to IVS2. 1. Mother: Heterozygous for c.46delT [Cod15 (-T)], 2. Patient: Homozygous pattern for c.46delT [Cod15 (-T)], 3. Father: Normal.
Source publication
Key Clinical Message
The beta thalassemia intermedia phenotype has several genotypes. Hematological and molecular diagnostic approach and logical and sequential conduct of various investigations are necessary for the diagnosis of these disorders. Close observations of the genotype–phenotype correlation will provide a better insight for the developm...
Context in source publication
Context 1
... showed that the mother is having a deletion of (-T) at codon 15 of the b-globin in a heterozygous state (leads to stop codon in 18th position [5]), the father had a normal pattern, and the patient showed a homozygous pattern for c.46delT [codon 15 (-T)] deletion, since he has two different deletions in each allele in the same genetic region (Fig. 3). ...
Citations
... The clinical severity of b-thal can be improved by the coinheritance of a-thalassemia (a-thal) [4,5]. The inheritance of a mild b-thal mutation is introduced by mutation on the b-globin chain [5] or by the coinheritance of a gene for hereditary persistence of fetal Hb (HPFH) [6,7]. Almost 300 b-thal alleles (point mutations) have so far been characterized [8]. ...
β-Thalassemia intermedia (β-TI) is a clinical condition characterized by moderate, non transfusional anemia and hepatosplenomegaly. The main objective of this study was to determine the molecular basis of the clinical phenotype of β-TI in Iran. To elucidate the mild phenotype of many patients with β-TI, we screened for three prevalent β-globin gene mutations [IVS-II-1 (G>A) HBB: c.315+1G>A, IVS-I-110 (G>A) HBB: c.93-21G>A and IVS-I-5 (G>C) [HBB: c.92+5G>C], deletions on the α-globin genes, XmnI polymorphisms and restriction fragment length polymorphism (RFLP) haplotypes on the β-globin gene cluster in 50 β-TI patients. Fifty-eight percent of the patients (29 cases) were associated with the mentioned mutations. We showed that the HBB: c.315+1G>A mutation is linked to haplotype [+ – + +] (57.69%). This haplotype is in linkage disequilibrium with the XmnI polymorphism (NG_000007.3: g.42677C>T) and has been associated with increased expression of Hb F in β-TI patients. The XmnI polymorphism is defined in association with this prevalent mutation. Two patients had a single α-globin gene deletion [–α3.7 (rightward) deletion]. The main genetic factor in mild phenotype β-TI patients is the linkage of an XmnI polymorphism (NG_000007.3: g.42677C>T) with the HBB: c.315+1G>A (80.76%), which is associated with increased production of Hb F and coinheritance of haplotype [+ – + +] with β-TI, especially with the homozygous HBB: c.315+1G>A mutation. Molecular basis of β-TI could be explained by the involvement of different factors that tend to develop the disease phenotype.
... It has a broad clinical spectrum, spanning in severity from asymptomatic thalassemia minor to transfusiondependent thalassemia major (TM) phenotype [4]. Thalassemia intermedia can result from the inheritance of one or two β-thal alleles [5][6][7][8]. On the other hand, no clinical significance have been observed for delta-globin (δ-globin) gene mutations, but this gene has important relevance for the screening of β-thal carriers [9]. ...
Background
Beta thalassemia (β-thal) is an inherited hemoglobin disorder characterized by reduced synthesis of the hemoglobin that results in microcytic hypochromic anemia. β-Thalassemia intermedia (TI) is a clinical term of intermediate gravity between the carrier state and β-thalassemia major (β -TM).
Case presentation
We describe a 12-year-old male proband originating from Al-Quneitra province - southwest Syria. Hematological investigations revealed, pallor and anemia (Hb 9 g/dl). The mean cell volume (MCV) 64 fL; mean cell hemoglobin (MCH) 21.8 pg. Capillary electrophoresis (CE) electropherogram revealed low level of Hb A1 (36.2%), high level of Hb F (62.2%) and low level of Hb A2 (1.6%). The proband requires blood transfusion occasionally. Direct DNA sequencing and Polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) for mutations detection were used. The molecular analysis revealed the presence of rare β⁺ Hb Knossos codon 27 (G > T) (HBB: c.82G > T) variant associated with β⁰ codon 5 [−CT] (HBB: c.17_18delCT) mutation in beta-globin (β-globin) gene and δ⁰ codon 59 [−A] (HBD: c.179delA) mutation in delta-globin (δ-globin) gene. The proband tested negative for the common deletional forms of alpha thalassemia (α-thal). Polymorphism of the Xmn-I locus (HBG2: c.-211C > T) revealed that the proband had a homozygous [TT] for Xmn-1 locus.
Conclusions
To our knowledge, this is the first report of beta thalassemia intermedia due to combination of Hb Knossos /codon 5 [−CT] associated with δ⁰ codon 59 [−A] in Syrian patient. On the other hand, in Syria, β-thal carriers who have low level of Hb A2 due to decreased δ-chain production, different δ-thal gene mutations must be screened to avoid the failure diagnosis of β-thal disease.
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Thalassemia is a genetic blood disorder that is autosomal recessive and is quite common throughout the world. This study aims to determine the relationship of Hemoglobin beta (HBB) gene mutations types with clinical levels and hematological in the subjects of 31 thalassemia-beta patients in Samarinda City. Blood samples were taken from patients to obtain their DNA then amplified them with the Polymerase Chain Reaction and direct sequencing techniques to analyze the hemoglobin-beta gene mutation. Javanese ethnics is the most dominant in this study (64.5%) and the most common clinical levels is the moderate category (77.4%). The mean MCV and MCH values were 72±5,5 fL and 24±3,3 pg. DNA analysis found 8 types of mutant alleles including 48.4% of Cd26 / HbE (GAG>AAG), 14.5% of IVS-1-5 (G>C) 12.9% of IVS-1-2 (T>C, ,8.1% of Cd35 (-C) , 6.5% of IVS-1-1 (G>T) 3.2% of Cd30 (AGG>ACG) , Cd60 (GTG>GAG) and Cd2 (CAT>CAC ) are 1.6% each. This study found mutations that had not been previously reported in Indonesia, namely Cd60 (GTG>GAG) and Cd2 (CAT>CAC). Spearman rank statistical tests show there is no significant relationship between the two studied variables.
Keyword: Beta-thalassemia mutation, Clinical levels, Hematological
Abstrak
Talasemia merupakan salah satu kelainan darah genetik yang bersifat autosomal resesif dan cukup banyak ditemui di seluruh dunia. Diperkirakan 3-10 persen masyarakat Indonesia adalah pembawa sifat talasemia dengan berbagai macam latar belakang etnik. Studi ini bertujuan untuk mengetahui hubungan jenis mutasi gen hemoglobin beta (HBB) dengan derajat klinis dan pemeriksaan darah pada 31 pasien talasemia-beta di Kota Samarinda Provinsi Kalimantan Timur pada bulan Mei tahun 2019. Sampel darah pasien diambil untuk memperoleh DNA kemudian dilakukan amplifikasi dengan Polymerase Chain Reaction dan dilakukan teknik direct sekuensing untuk menganalisis mutasi gen hemoglobin-beta. Etnik Jawa merupakan yang dominan dalam penelitian ini (64,5%) dan derajat klinis paling umum adalah kategori sedang (77,4%). Rerata nilai MCV dan MCH masing-masing adalah 72±5,5 fL dan 24±3,3 pg. Analisa DNA didapatkan 8 jenis alel mutan yaitu Cd26/HbE (GAG>AAG) 48,4% selanjutnya IVS-1-5 (G>C) 14,5%, IVS-1-2 (T>C) 12,9%, Cd35 (-C) 8,1%, IVS-1-1 (G>T) 6,5%, Cd30 (AGG>ACG) 3,2%, Cd60 (GTG>GAG) dan Cd2 (CAT>CAC) masing-masing 1,6%. Studi ini menemukan mutasi yang belum dilaporkan pada penelitian sebelumnya di Indonesia yaitu Cd60 (GTG>GAG) dan Cd2 (CAT>CAC). Uji statistik spearman rank menunjukkan tidak terdapat hubungan bermakna antara ke dua variabel yang diteliti.
Kata kunci: Mutasi talasemia beta, Derajat klinis, Hematologis
