Hb DARTMOUTH [α66(E15)Leu → Pro (α2) (CTG → CCG)]: A NOVEL α2-GLOBIN GENE MUTATION ASSOCIATED WITH SEVERE NEONATAL ANEMIA WHEN INHERITED IN TRANS WITH SOUTHEAST ASIAN α-THALASSEMIA-1

Hemoglobin ◽  
2001 ◽  
Vol 25 (4) ◽  
pp. 375-382 ◽  
Author(s):  
Kim L. McBride ◽  
Karen Snow ◽  
Kathleen S. Kubik ◽  
Virgil F. Fairbanks ◽  
James D. Hoyer ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Globin Gene ◽  
Southeast Asian ◽  
In Trans

scholarly journals Genetic research and clinical analysis of deletional Chinese Gγ+(Aγδβ)0 -thalassemia and Southeast Asian HPFH in South China

2020 ◽  
Vol 99 (12) ◽  
pp. 2747-2753
Author(s):  
Yuanjun Wu ◽  
Qianyu Yao ◽  
Ming Zhong ◽  
Jianying Wu ◽  
Longxu Xie ◽  
...  
Keyword(s):  
Gene Mutation ◽  
South China ◽  
Hematological Parameters ◽  
Globin Gene ◽  
Genetic Research ◽  
Fetal Hemoglobin ◽  
Clinical Analysis ◽  
Southeast Asian ◽  
Mean Corpuscular Hemoglobin ◽  
Phenotypic Analysis

AbstractChinese Gγ+(Aγδβ)0-thalassemia and SEA-HPFH are the most common types of β-globin gene cluster deletion in Chinese population. The aim of the study was to analyze clinical features of deletional Chinese Gγ+(Aγδβ)0-thalassemia and Southeast Asian hereditary persistence of fetal hemoglobin (SEA-HPFH) in South China. A total of 930 subjects with fetal hemoglobin (HbF) level ≥ 2% were selected on genetic research of Chinese Gγ+(Aγδβ)0-thalassemia and SEA-HPFH. The gap polymerase chain reaction was performed to identify the deletions. One hundred cases of Chinese Gγ+(Aγδβ)0-thalassemia were detected, including 90 cases of Chinese Gγ+(Aγδβ)0/βN-thalassemia, 7 cases of Chinese Gγ+(Aγδβ)0 /βN-thalassemia combined with α-thalassemia, 2 cases of Chinese Gγ+(Aγδβ)0-thalassemia combined with β-thalassemia, and 1 case of Chinese Gγ+(Aγδβ)0-thalassemia combined with β-gene mutation. One hundred nine cases of SEA-HPFH were detected, including 97 cases of SEA-HPFH/βN, 9 cases of SEA-HPFH/βN combined with α-thalassemia, 2 cases of SEA-HPFH combined with β-thalassemia, and 1 case of SEA-HPFH combined with β-gene mutation. Statistical analysis indicates significant differences in MCV (mean corpuscular volume), MCH (mean corpuscular hemoglobin), and HbA2 and HbF levels between Chinese Gγ+(Aγδβ)0-thalassemia heterozygotes and SEA-HPFH heterozygotes (P < 0.001). There are statistical differences in hematological parameters between them. Clinical phenotypic analysis can provide guidance for genetic counseling and prenatal diagnosis.

A silencer element from the alpha-globin gene inhibits expression of beta-like genes

1988 ◽  
Vol 8 (11) ◽  
pp. 5047-5051
Author(s):  
G F Atweh ◽  
J M Liu ◽  
H E Brickner ◽  
X X Zhu
Keyword(s):  
Globin Gene ◽  
Expression System ◽  
Globin Genes ◽  
Beta Globin ◽  
Base Pair Fragment ◽  
Alpha Globin ◽  
In Trans ◽  
Cis And Trans ◽  
In Cis ◽  
Silencer Element

We have studied the cis and trans interactions of the alpha- and beta-globin genes in a transient expression system. We found that the alpha-globin gene inhibited beta-globin expression in cis but not in trans. The silencer element responsible for this inhibition was localized to a 259-base-pair fragment at the 5' end of the alpha-globin gene.

scholarly journals Multiplex Minisequencing Screen for Common Southeast Asian and Indian β-Thalassemia Mutations

2003 ◽  
Vol 49 (2) ◽  
pp. 209-218 ◽  
Author(s):  
Wen Wang ◽  
Shirley K Y Kham ◽  
Gare-Hoon Yeo ◽  
Thuan-Chong Quah ◽  
Samuel S Chong
Keyword(s):  
Globin Gene ◽  
Scale Up ◽  
Gene Mutations ◽  
Population Based ◽  
Southeast Asian ◽  
Wild Type ◽  
Specific Primers ◽  
Double Blind ◽  
Mutation Site ◽  
Single Nucleotide

Abstract Background: β-Thalassemia is endemic to many regions in Southeast Asia and India, and &lt;20 β-globin gene mutations account for ≥90% of β-thalassemia alleles in these places. We describe a multiplex minisequencing assay to detect these common mutations. Methods: Gap-PCR was used to simultaneously amplify the β-globin gene from genomic DNA and to detect the Δ619bp deletion mutation. Multiplex minisequencing was then performed on the amplified β-globin fragment to detect an additional 15 common Southeast Asian and Indian β-thalassemia mutations. Site-specific primers of different lengths were subjected to multiple rounds of annealing and single-nucleotide extension in the presence of thermostable DNA polymerase and the four dideoxynucleotides, each labeled with a different fluorophore. Minisequencing products were separated and detected by capillary electrophoresis, followed by automated genotyping. The optimized assay was subjected to a double-blind validation analysis of 89 β-thalassemia and wild-type DNA samples of known genotype. Results: Homozygous wild-type or mutant DNA samples produced electropherograms containing only a single colored peak for each mutation site, whereas samples heterozygous for a specific mutation displayed two different-colored peaks for that mutation site. Samples were automatically genotyped based on color and position of primer peaks in the electropherogram. In the double-blind validation analysis, all 89 DNA samples were genotyped correctly (100% assay specificity). Conclusions: The described semiautomated multiplex minisequencing assay can detect the most common Southeast Asian and Indian β-thalassemia mutations, is amenable to high-throughput scale up, and may bring population-based screening of β-thalassemia in endemic regions a step closer to implementation.

scholarly journals Observations on the levels of Hb A2 in patients with different beta- thalassemia mutations and a delta chain variant

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1246-1249 ◽  
Author(s):  
JF Codrington ◽  
HW Li ◽  
F Kutlar ◽  
LH Gu ◽  
M Ramachandran ◽  
...  
Keyword(s):  
Promoter Activity ◽  
Globin Gene ◽  
Gene Promoter ◽  
General Mechanism ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Beta Chain ◽  
Beta Globin Gene ◽  
In Trans ◽  
In Cis

Abstract Hb A2 and its variant B2 (alpha 2 delta 2(16)(A13)Gly----Arg) were quantitated in the blood of subjects with three different types of beta- thalassemia and with the delta-B2 anomaly in cis or in trans to the beta-thalassemia determinant. In one family, the delta-B2 mutation was in cis to a newly discovered codon 47 (+A) frameshift. The levels of Hbs A2 and B2 were nearly the same and approximately 70% higher than those in simple Hb B2 heterozygotes. In two additional families, the delta-B2 variant was in trans to either a deletional beta-thalassemia (1,393 bp) involving part of the beta-globin gene and part of the beta- globin gene promoter, or to the -88 C----T promoter mutation. In both instances, the Hb B2 level was increased by approximately 80%, but the Hb A2 level was increased by approximately 270% and 200%, respectively. These data indicate two mechanisms that will cause an increase in delta chain production. One is consistent with a general mechanism concerning the relative excess of alpha chains in beta chain deficiencies which will combine with delta chains to form variable levels of Hb A2 dependent on the severity of the beta chain deficiency. The second concerns the loss of beta-globin gene promoter activity, perhaps by an absence of (or decreased) binding of specific protein(s) to this segment of DNA and a concomitant increase in delta-globin gene promoter activity in cis.

Haplotype Analysis in Carriers of β-globin Gene Mutation Facilitates Genetic Counseling in β-thalassemia: A Cross-Sectional Study in Kerman Province, Iran

2020 ◽  
Author(s):  
Nasrollah SALEH-GOHARI ◽  
Kolsoum SAEIDI ◽  
Sima ZIAADINI-DASHTKHAKI
Keyword(s):  
Genetic Counseling ◽  
Gene Mutation ◽  
Haplotype Analysis ◽  
Globin Gene ◽  
Mutation Screening ◽  
Hypochromic Anemia ◽  
Cross Sectional Study ◽  
Common Mutation ◽  
Sectional Study ◽  
Cross Sectional

Background: β-thalassemia is characterized by reduced synthesis of the hemoglobin beta chain that results in microcytic hypochromic anemia and reduced amounts of hemoglobin A (HbA) on hemoglobin analysis. β-thalassemias are caused by mutations in the β-globin gene, inherited in an autosomal recessive manner. Determining molecular defects in couples carrying β-thalassemia is a prerequisite for prenatal diagnosis of the disease. In this regards, database of β-globin gene haplotypes facilitates mutation detection of the gene and helps genetic counselors to reach the goals of β-thalassemia prevention program. Methods: In this cross-sectional study, 255 couples attended genetic counseling between December 2017 and January 2019 in Afzalipour Hospital, Kerman University of Medical Scinces, Kerman, Iran as suspicious of βthalassemia carriers. Furthermore, they were investigated using amplification refractory mutations system-polymerase chain reaction and restriction fragment length polymorphism methods for mutation screening and haplotype analysis of polymorphic sites in β-globin gene cluster, respectively. Results: We identified 20 different types of β-globin gene mutation in 449 β-thalassemia carriers. Analysis of the pattern of Hind III/Gγ, Hinf I/5′β, Hinc II/3′Ψβ, Rsa I/5′β, AvaII/β and Hind III/Aγ polymorphic sites in 257 alleles of informative families revealed 17 different haplotypes. Haplotype 1 (77.24%) showed strong linkage with the most common mutation IVSI-5 while haplotype 5 (66.67%) was associated with the second frequent mutation IVSII-1. Conclusion: To our knowledge, these β-globin haplotypes are reported for the first time which are different with those found in other parts of Iran. The current haplotypes pattern data makes the counseling of β-thalassemia carriers more straightforward and the process of mutation screening faster and more accurate.

De novoβ-globin gene mutation [β63(E7)HIS→TYR] giving rise to Hb M disease in a newfoundlander

Hemoglobin ◽  
1994 ◽  
Vol 18 (6) ◽  
pp. 441-443
Author(s):  
J. S. Waye ◽  
M. Patterson ◽  
B. Eng
Keyword(s):  
Gene Mutation ◽  
Globin Gene
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