First Observation of Hemoglobin G-Waimanalo and Hemoglobin Fontainebleau Cases in the Turkish Population (original) (raw)
Hb Narges Lab, a Novel Hemoglobin Variant of the β-Globin Gene
Archives of Iranian Medicine
In this study, we describe a new missense variant on the β-globin gene in a heterozygous form in a female individual. Standard methods were used to determine red blood cell indices and perform hemoglobin analyses. Molecular studies were performed on the genomic DNA isolated from peripheral blood cells. Beta-globin genes were amplified and sequenced. We report a novel mutation on the β-globin gene (HBB), c.134 C>T; p.S44F variant, in the heterozygote state which was detected in a female of Persian ethnic origin in the Khuzestan province, southern Iran, that we named Hb Narges Lab (HbNL) variant. This mutation was predicted to be disease-causing in all except one in silico prediction tools. This variant was reported for the first time worldwide, had no shown hematological abnormalities but should be considered when inherited in the compound heterozygous form with β- thalassemia (β0-thal) carrier, which might result in the phenotype of thalassemia intermedia.
Abnormal hemoglobins associated with the beta-globin gene in Antalya province, Turkey
journals.tubitak.gov.tr
Abnormal hemoglobins are the most common hemoglobinopathies after beta-thalassemia in the world. More than 40 abnormal hemoglobin variants have been reported in the Turkish population. Therefore, it is one of the target areas for carrier screening. In our study, we aimed to screen the abnormal hemoglobins that cause clinical thalassemia in the Antalya population. Materials and methods: The present study identified the abnormal hemoglobins associated with the beta-globin gene using different molecular genetic techniques following high performance liquid chromatography (HPLC) results. We studied 972 postnatal and 361 prenatal cases (total: 1333 cases, 2666 chromosomes) with the disorder from 1998 up to July 2008. DNA extraction from peripheral blood, chorionic villi samples (CVS), amniotic cells, and cord blood samples was carried out using standard procedures. Following polymerase chain reaction (PCR) and amplification of the betaglobin gene, allele refractory mutation system (ARMS), reverse dot blot hybridization (RDBH), Nanochip, and DNA sequencing were performed to identify the mutations. Variable number of tandem repeats (VNTR) analysis was used for elimination of maternal contamination in prenatal diagnosis. We identified and characterized abnormal hemoglobin variants with novel and rare beta-thalassemic mutations.
OAlib, 2016
Background: Presentation of the first case of beta-thalassemia compound heterozygous with known mutations. Case Report: The patient was 3 years old girl. First symptoms were cough, fatigue, paleness. Hepatosplenomegaly were determined. Hematology parameters were: RBC 1.79 M/uL, Hb4.6 g/dL, Hct 12.3%, MCV 68.7fL, MCH 25.7pg, RDW 31.5%. The level of hemoglobin variants was: HbF 80.5%, HbA 18.2%, HbA2 1.3%, and by molecular analysis codon 8 (-AA) and codons 22/23/24(-AAGTTGG) compound heterozygous mutations were detected. Codon 8 (-AA) and codons 22/23/24(-AAGTTGG) heterozygous mutations were also detected in patient's mother and father respectively. Conclusion: Clinical manifestations such as late onset of symptoms and laboratory findings of patient with compound heterozygous deletion mutation were worse than homozygous patients whom are having the same mutations. It is important that the detection of carriers before the marriage to prevent the birth of patient children and genetic counseling is a good variety of ways of informing the public on the importance of prenatal diagnosis.
Identification of patients with defects in the globin genes
Journal of Prenatal Medicine, 2013
hemoglobinopathies constitute a major health problem worldwide. These disorders are characterized by a clinical and hematological phenotypic heterogeneity. The increase of HbA2 is an invaluable hematological marker of the beta-thalassemia heterozygosis and of double heterozygosis for the alleles of delta and alpha globin genes or for the alleles of delta and beta globin genes which can cause the increase of HbA2 up to normal or borderline values. we report the case of a 30-year-old woman (first pregnant) who was admitted to our Unit at 12 weeks for a screening for thalassemia. The outcomes of the biochemical and haematological exams (MCV, MCH, HbA2, HbF) highlighted that the patient was a carrier of a beta-thalassemic trait. Molecular analysis of the beta globin genes highlighted a β(0)39C>T heterozygous mutation. Biochemical and hematological parameters of the husband (MCV, MCH, HbA2, HbF) were normal except for the level of HbA2 (3,6%). The molecular analysis of the beta globin...
Analysis of beta globin gene mutations in Diyarbakir
Turkish Journal of Biochemistry
Objectives Hemoglobin disorders are quite heterogeneous in the Turkish population. Up to now, more than forty different beta thalassemia mutations and 60 hemoglobin variants have been characterized in the country. The aim of this study was to investigate genetic heterogeneity of HBB gene mutations in patients and their parents at Southeastern Anatolia in Turkey. Methods Genomic DNA was isolated from 145 thalassemic patients’ blood samples and their parents in this study. Ten different HBB gene mutations HBB:c.-80T>A, HBB:c.17_18delCT, HBB:c.25_26delAA, HBB:c.92+1G>A, HBB:c.92+5G>C, HBB:c.92+6T>C, HBB:c.93-21G>A, HBB:c.135delC, HBB:c.315+1G>A, HBB:c.316-106C>G were screened by amplification refractory mutation system. Four Hb variants and some rare beta thalassemia mutation were characterized by DNA sequencing. Results In this study, 97 homozygous and 48 compound heterozygous thalassemic patients were diagnosed by molecular genetic analyses. As a results, 18 β-th...
Journal of Hematological Malignancies, 2013
Introduction: hemoglobinopathies constitute a major health problem worldwide. These disorders are characterized by a clinical and hematological phenotypic heterogeneity. The increase of HbA2 is an invaluable hematological marker of the beta-thalassemia heterozygosis and of double heterozygosis for the alleles of delta and alpha globin genes or for the alleles of delta and beta globin genes which can cause the increase of HbA2 up to normal or borderline values. Case Report: we report the case of a 30-year-old woman (first pregnant) who was admitted to our Unit at 12 weeks for a screening for thalassemia. The outcomes of the biochemical and haematological exams (MCV, MCH, HbA2, HbF) highlighted that the patient was a carrier of a beta-thalassemic trait. Molecular analysis of the beta globin genes highlighted a β 0 39C>T heterozygous mutation. Biochemical and hematological parameters of the husband (MCV, MCH, HbA2, HbF) were normal except for the level of . The molecular analysis of the beta globin genes highlighted a IVS2 nt844 C>G heterozygous mutation. Furthermore, the heterozygous mutation δ + cod.27G>T was detected in his δ globin gene. For this reason, he was diagnosed a δ+β Thal. Conclusions: the aim of this paper is to highlight that biochemical diagnosis could not exhaustive and a molecular diagnostic widening is required to detect the genetic deficiency causing the thalassemic trait.
Journal of Clinical & Biomedical Research, 2022
Hemoglobinopathies are a major health problem worldwide. These disorders are characterized by a variable clinical and hematological situation related to a phenotypic heterogeneity. Moreover, in order to have an exact correlation between the biochemical picture and the genetic defect associated with it, it is useful and often indispensable the molecular study of alpha and beta globin genes. The present case report concerns a pregnant woman of Moroccan ethnicity who came to our observation to undergo combined first-trimester testing useful for screening of major chromosomal aneuploidies. Study of hemoglobins A, A2, and F by High performance liquid chromatography (HPLC) revealed the presence of a proportion of abnormal hemoglobin associated with hemoglobin S. Molecular investigation of globin genes excluded that the biochemical variant in question was related to hemoglobin S. In fact, molecular investigation of beta globin genes, found that the observed variant was due to the presence of a genetic defect leading to hemoglobin O Arab synthesis. Evidence suggests that molecular analysis of globin genes provides the most effective and correct way to correlate the detected biochemical picture with its associated genetic defect. The only biochemical study in the presented case determines an incorrect clinical evaluation with consequent inaccurate prognosis. The mutation detected in this work can be identified using a simple and inexpensive kit. This would generate, in economic terms, significant savings associated with a correct diagnosis.
European Journal of Haematology, 2010
Nowadays, haemoglobinopathies are the most common recessive traits in rapidly evolving multiethnic societies, and a correct diagnosis of these diseases are a matter of concern in many countries organising prevention either at the preconception level, in early pregnancy or after neonatal screening (1). Many problems are associated with the different interventions, and the recognition of the carriers at the laboratory level is one of them. Analysis based on haemoglobin (Hb) separation methods is reliable for the recognition of the common traits and diseases associated with Hbs S [b6(A3)Glu fi Val], C [b6(A3)Glu fi Lys], E [b26(B8)Glu fi Lys], D Punjab [b121(GH4) GlufiGln] and high Hb A 2 b-thalassaemia (b-thal). However, although the degree of sensitivity and specificity is high, provisional results have to be confirmed at the molecular level, especially in case of risk assessment or treatment. Moreover, carriers of these traits are usually not, or just slightly, anaemic, and this will prevent these carriers from being selected for laboratory analysis in the preconception phase, unless the local general practitioner also considers ethnic origin as an indication for carrier analysis (1). Because in most European countries the main reason for referral to the local laboratories is microcytic hypochromic anaemia not responding to iron therapy, the laboratories will usually identify carriers of high Hb A 2 b-thal and suspect a-thal carriers, but carriers of one of the common abnormal Hbs mentioned earlier will be referred for analysis only when associated with some anaemia which is mostly because of a coexisting a-thal.