scholarly journals Splice-site and Frameshift Mutations of β-Globin Gene Found in Thalassemia Carrier Screening in Yogyakarta Special Region, Indonesia

2021 ◽  
Vol 13 (1) ◽  
pp. 55-60
Author(s):  
Niken Satuti Nur Handayani ◽  
Nailil Husna ◽  
Gunawan Rahmil ◽  
Riris Anindya Ghifari ◽  
Lily Widyawati ◽  
...  
Keyword(s):  
Splice Site ◽  
Prevention Program ◽  
Screening Program ◽  
Globin Gene ◽  
Carrier Screening ◽  
Amplification Refractory Mutation System ◽  
Frameshift Mutations ◽  
Blood Disorder ◽  
Thalassemia Screening ◽  
Special Region

BACKGROUND: β-thalassemia is an inherited blood disorder that relatively common in Southeast Asian countries. In Indonesia, it is estimated that 200,000 infants with thalassemia carrier born each year. Mutation causing β-thalassemia is highly varied and relatively specific in a population. This study aimed to identify the mutations responsible for β-thalassemia from Thalassemia Carrier Screening conducted in Yogyakarta Special Region. This information is beneficial for developing a strategic prevention program to control thalassemia in the region.METHODS: Twenty-eight blood samples of haematologically suspected β-thalassemia from participant of thalassemia screening program in Yogyakarta Special Region were investigated for β-globin gene mutation by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), amplification refractory mutation system (ARMS) and DNA sequencing.RESULTS: Our samples showed average HbA2 value of 5±0.81% and HbF value of 2±2.29%. It showed eight abnormal erythrocyte morphologies dominated by hypochromia (96.4%), cigar cell (85.7%), and microcytosis (78.6%). Our molecular investigation identified three splice-site mutations namely InterVening Sequence (IVS)-1-5 (G>C) (71.4%), IVS-1-2 (T>C) (7.1%), and IVS-1-1 (G>T) (3.6%), two frameshift mutations that are CD35 (-C) (10.7%) and CD8/9 (+G) (3.6%), and a missense mutation of CD6 (GAG>GTG) (3.6%).CONCLUSION: Our study concluded on a high prevalence of IVS-1-5 (G>C) mutation in Yogyakarta Special Region. This mutation information is significant for developing a strategic prevention program to control thalassemia in the region, for example for developing a rapid molecular test for future screening program.KEYWORDS: β-Globin gene, thalassemia, screening, carrier, mutation, Yogyakarta

Identification of deletion and triple α-globin gene haplotypes in the montreal β-thalassemia screening program: Implications for genetic medicine

1990 ◽  
Vol 36 (1) ◽  
pp. 76-84 ◽  
Author(s):  
Beverly R. Akerman ◽  
T. Mary Fujiwara ◽  
Gerald A. Lancaster ◽  
Kenneth Morgan ◽  
Charles R. Scriver
Keyword(s):  
Screening Program ◽  
Globin Gene ◽  
Genetic Medicine ◽  
Thalassemia Screening

scholarly journals In silico prediction of HBD gene variants in the Iranian population

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Keivan Moradi ◽  
Aboozar Mohammadi ◽  
Mohsen Kazeminia
Keyword(s):  
Persian Gulf ◽  
Globin Gene ◽  
Iranian Population ◽  
Gene Variants ◽  
In Silico Prediction ◽  
Screening Programs ◽  
Prediction Tools ◽  
Clinical Laboratories ◽  
The Persian Gulf ◽  
Thalassemia Screening

Abstract Background The quantification of hemoglobin A2 (Hb A2; α2δ2) is used as a valuable test to differentiate α- and ß-thal carriers in clinical laboratories. Therefore, the HBD (δ-globin) gene variants could result in reduced levels of Hb A2 and have implications for thalassemia screening programs. The aim of the present study was to predict the consequences of HBD gene variants identified in the Iranome project. Results The highest number of variants was in the Persian Gulf Islanders. The variants of p.Gln132Glu (HBD: c.394C>G), p.Gly17Arg (HBD: c.49G>C), p.Thr5Ile (HBD: c.14C>T), and p.Ala28Ser (HBD: c.82G>T) presented damage results in three or more prediction tools. In addition, it seems that the p.Gly30= (HBD: c.90C>T) decreases the use of authentic splice and, instead, creates a new donor splice site (DSS) or leads to the use of a cryptic DSS. Conclusions Most of these variants have been associated with a decrease in Hb A2 levels. Due to the high mutational diversity in the HBB gene in the Iranian population and the use of Hb A2 quantification to differentiate α- and ß-thal carriers among Iranian clinical laboratories, some attention should be taken to a possible co-inheritance of HBD gene variants to avoid the misdiagnosis of ß-thal carriers.

scholarly journals Evaluation of Technical Issues in a Pilot Multicenter Newborn Screening Program for Sickle Cell Disease

2018 ◽  
Vol 5 (1) ◽  
pp. 2
Author(s):  
Maddalena Martella ◽  
Giampietro Viola ◽  
Silvia Azzena ◽  
Sara Schiavon ◽  
Andrea Biondi ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Newborn Screening ◽  
Molecular Analysis ◽  
Sickle Cell ◽  
Screening Program ◽  
Globin Gene ◽  
False Negative ◽  
Confirmatory Test ◽  
Cell Disease ◽  
Technical Issues

A multicenter pilot program for universal newborn screening of Sickle cell disease (SCD) was conducted in two centres of Northern Italy (Padova and Monza). High Performance Liquid Chromatography (HPLC) was performed as the first test on samples collected on Guthrie cards and molecular analysis of the β-globin gene (HBB) was the confirmatory test performed on the HPLC-positive or indeterminate samples. 5466 samples of newborns were evaluated. Of these, 5439/5466 were submitted to HPLC analysis and the molecular analysis always confirmed in all the alteration detected in HPLC (62/5439 newborns); 4/5439 (0.07%) were SCD affected, 37/5439 (0.68%) were HbAS carriers and 21/5439 (0.40%) showed other hemoglobinopathies. Stored dried blood spots were adequate for HPLC and β-globin gene molecular analysis. Samples were suitable for analysis until sixteen months old. A cut-off of A1 percentage, in order to avoid false negative or unnecessary confirmation tests, was identified. Our experience showed that several technical issues need to be addressed and resolved while developing a multicenter NBS program for SCD in a country where there is no national neonatal screening (NBS) program for SCD and NBS programs occur on a regional basis.

Identification of a new β-thalassaemia variant Term CD+32(HBB: c.32A>C) in two Chinese families

2020 ◽  
Vol 73 (9) ◽  
pp. 593-596
Author(s):  
Jianlong Zhuang ◽  
Yu Zheng ◽  
Yuanbai Wang ◽  
Qianmei Zhuang ◽  
Yuying Jiang ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Elevated Level ◽  
Globin Gene ◽  
Novel Mutations ◽  
Fujian Province ◽  
Chinese Families ◽  
Rare Mutation ◽  
Direct Dna Sequencing ◽  
Her Family ◽  
Blood Disorder

Aimsβ-Thalassaemia is an inherited blood disorder caused by mutations in the β-globin gene cluster. Molecular characterisation of β-thalassaemia is essential for its diagnosis and management. More and more rare and novel mutations have been reported.MethodsTwo Chinese families with β-thalassaemia from Fujian Province were recruited in this study. The phenotypes of the probands were confirmed through haematological analysis. Routine molecular analysis of thalassaemia was employed to identify the common mutations of thalassaemia. The rare and novel mutations were detected by direct DNA sequencing.ResultsIn family 1, the proband, a Chinese woman aged 31 years, showed elevated level of haemoglobin A2 (HbA2). No common mutations associated with β-thalassaemia were detected, whereas a rare mutation Term CD+32(HBB: c.32A>C) was identified through DNA sequencing. Subsequent investigation of the β-thalassaemia mutation in her family showed that her mother, her brother as well as her nephew also carried this mutation. In addition, both the proband’s husband and her son carrying the rare --THAI mutation exhibited decreased levels of MCH, MCH and HbA2. In family 2, the proband, a child aged 1 year, showed elevated level of HbA2, but had no common mutations of β-thalassaemia. The proband was identified carrying the mutation Term CD+32(HBB: c.32A>C), which was inherited from his mother.ConclusionsIn this study, we first report a rare β-thalassaemia mutation in Fujian Province, Southeast China. Moreover, our study also identified this rare mutation in humans. This finding has helped broaden the spectrum of β-thalassaemia mutations in our region and suggested that this rare mutation may be more prevalent in the Chinese population.

Genetic epidemiology of beta-thalassemia in the Maldives: 23 years of a beta-thalassemia screening program

Gene ◽  
2020 ◽  
Vol 741 ◽  
pp. 144544
Author(s):  
Ibrahim Mustafa ◽  
Naila Firdous ◽  
Fatma M. Shebl ◽  
Zumin Shi ◽  
Mariya Saeed ◽  
...  
Keyword(s):  
Genetic Epidemiology ◽  
Screening Program ◽  
Beta Thalassemia ◽  
Thalassemia Screening

Alpha Globin Gene Mutation: A Major Determinant of Hydroxyurea Response in Transfusion-Dependent HbE-β-Thalassaemia

2019 ◽  
Vol 142 (3) ◽  
pp. 132-141
Author(s):  
Sujana Biswas ◽  
Rudra Ray ◽  
Kaushik Roy ◽  
Anish Bandyopadhyay ◽  
Kanjaksha Ghosh ◽  
...  
Keyword(s):  
Single Gene ◽  
Globin Gene ◽  
Poor Responders ◽  
Amplification Refractory Mutation System ◽  
Gene Deletions ◽  
Globin Chains ◽  
Hydroxyurea Treatment ◽  
Transfusion Requirements ◽  
F Cells ◽  
Alpha Globin

Thalassaemias are the most common inherited autosomal recessive single gene disorders characterised by chronic hereditary haemolytic anaemia due to absence or reduced synthesis of one or more of the globin chains. Haemoglobin E (HbE)-β-thalassaemia is the genotype responsible for approximately one-half of all cases of severe β-thalassaemia worldwide. This study proposes to evaluate response of hydroxyurea in reducing transfusion requirements of severe HbE-β-thalassaemia patients, and its correlation with foetal haemoglobin (HbF) level and α-mutation. Hydroxyurea was started at a baseline dose in 82 transfusion-dependent HbE-β-thalassaemia patients. HbF levels and %F-cells were measured. β-Thalassaemia mutations and α-globin gene deletions and triplications were detected by amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR) and Gap-PCR, respectively. Patients were categorised as good (41.5%), moderate (31.7%), and poor responders (26.8%) based on their decrease in transfusion requirements. Nine patients were excellent responders who became transfusion independent. The mean increase in HbF levels and %F-cells after therapy was correlated with decrease in transfusion requirements. Patients having a deletion of the α-globin gene were better responders. The response was proportional to the number of α-globin gene deletions. We conclude that hydroxyurea treatment decreases transfusion requirements, and the response correlates with α-globin gene deletions.

A Further case of β-Thalassemia with an Homozygous T→C Substitution at the Donor Splice Site of the First Intervening Sequence of the β-Globin Gene

Hemoglobin ◽  
1989 ◽  
Vol 13 (6) ◽  
pp. 619-621 ◽  
Author(s):  
A. M. Lossi ◽  
M. Milland ◽  
J. L. Bergé-Lefranc ◽  
D. Lena-Russo ◽  
H. Perrimond
Keyword(s):  
Splice Site ◽  
Globin Gene ◽  
Donor Splice Site ◽  
Donor Splice

scholarly journals The impact of a national population carrier screening program on cystic fibrosis birth rate and age at diagnosis: Implications for newborn screening

2016 ◽  
Vol 15 (4) ◽  
pp. 460-466 ◽  
Author(s):  
Patrick Stafler ◽  
Meir Mei-Zahav ◽  
Michael Wilschanski ◽  
Huda Mussaffi ◽  
Ori Efrati ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Newborn Screening ◽  
Birth Rate ◽  
Screening Program ◽  
Carrier Screening ◽  
Age At Diagnosis ◽  
National Population ◽  
The Impact

EE score: an index for simple differentiation of homozygous hemoglobin E and hemoglobin E-β0-thalassemia

2018 ◽  
Vol 56 (9) ◽  
pp. 1507-1513 ◽  
Author(s):  
Kritsada Singha ◽  
Goonnapa Fucharoen ◽  
Kanokwan Sanchaisuriya ◽  
Supan Fucharoen
Keyword(s):  
Predictive Value ◽  
Dna Analysis ◽  
Screening Program ◽  
Inverse Correlation ◽  
Molecular Testing ◽  
Related Disorder ◽  
Hemoglobin E ◽  
Dna Analyses ◽  
Homozygous Hemoglobin E ◽  
Thalassemia Screening

Abstract Background: The objective of the study was to describe a formula based on hemoglobin (Hb)A2 and HbF levels for differentiation of homozygous HbE and HbE-β-thalassemia. Methods: A total of 1256 subjects suspected for homozygous HbE or HbE-β0-thalassemia were recruited at the ongoing thalassemia screening program at Khon Kaen University, Thailand. Hb analysis was done using capillary electrophoresis. Genotyping was based on DNA analysis. An arbitrary formula based on HbA2 and HbF was developed statistically for differentiation of the two conditions. Validation was carried out prospectively on another 139 subjects encountered at routine laboratory. Results: Among 1256 subjects, Hb and DNA analyses identified cases with homozygous HbE (n=1076, 85.7%), HbE-β0-thalassemia (n=140, 11.1%), HbE-δβ0-thalassemia (n=30, 2.4%) and unknown HbE-related disorder (n=10, 0.8%). An inverse correlation between the amounts of HbA2 and HbF in HbE-β0-thalassemia was observed. With differences in the amounts of HbA2 and HbF between the groups, an arbitrary score (7.3 HbA2+HbF) was developed where score above 60 indicated HbE-β0-thalassemia. Application of this score on another 139 subjects showed accurate prediction of HbE-β0-thalassemia with 100% sensitivity, 96.5% specificity, 85.7% positive predictive value and 100% negative predictive value. Successful application onto couples at risk was demonstrated. Conclusions: An established score should prove useful in the differentiation of homozygous HbE and HbE-β0-thalassemia in routine setting and lead to a significant reduction in number of referring cases for molecular testing.

scholarly journals Analysis of beta globin gene mutations in Diyarbakir

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Selahaddin Tekeş ◽  
Diclehan Oral ◽  
Murat Söker ◽  
Selda Şimşek ◽  
Veysiye Hülya Uzel ◽  
...  
Keyword(s):  
Globin Gene ◽  
Molecular Genetic ◽  
Point Mutations ◽  
Gene Mutations ◽  
Turkish Population ◽  
University Hospital ◽  
Beta Thalassemia ◽  
Amplification Refractory Mutation System ◽  
Compound Heterozygous ◽  
Common Mutation

Abstract 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-thalassemia mutations and four abnormal hemoglobins; HBB:c.20A>T, HBB:c.364G>C, HBB:c.34G>A and HBB:c.208G>A were detected at Dicle University Hospital. Conclusions In the results, HBB:c.93-21G>A is the most common mutation in the region. Three mutations [(HBB:c.93-21G>A), (HBB:c.25_26delAA) and (HBB:c.135delC)] account for about 58 per cent of all the point mutations. Except HBB:c.20A>T and HBB:c.364G>C, two silent Hb variants (HBB:c.34G>A and HBB:c.208G>A) were detected in this study. Hb Hamilton [β11 (GTT>ATT) Val>Ile] was seen first time in Turkey.

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