Genetic Factors Affecting Clinical Severity in β-Thalassemia Syndromes
ชื่อเรื่อง
Genetic Factors Affecting Clinical Severity in β-Thalassemia Syndromes
See all items with this value
ผู้สร้าง/เจ้าของผลงาน
Winichagoon, Pranee
See all items with this value
See all items with this value
Fucharoen, Suthat
See all items with this value
See all items with this value
Chen, Ping
See all items with this value
See all items with this value
Wasi, Prawase
See all items with this value
หัวเรื่อง
Thalassemia
See all items with this value
คำอธิบายรายละเอียดของเอกสาร
This study was Supported by grants from the National Research Council of Thailand, International Atomic Energy Agency, and Prajadhipok-Rambhai Barni Foundation.
บทคัดย่อ
Purpose
Heterogeneity in the clinical manifestation of β-thalassemic diseases may occur from the nature of β-globin gene mutations, α-thalassemia gene interaction, or differences in the amount of hemoglobin (Hb) F production. This study was conducted to determine whether these genetic determinant factors can predict phenotypic severity of patients with β-thalassemia and to assess the relationship between the genotype and phenotype of the disease.
Materials and Methods
A total of 144 patients with β-thalassemia were divided into mild (46 patients), intermediate (55 patients), and severe groups (43 patients). DNA analysis based on polymerase chain reaction technique was performed to characterize types of β-thalassemia mutation, interaction of α-thalassemia, and Xmn I polymorphism 5´ to Gγ-globin gene.
Results
Two alleles of mild β-thalassemia mutation (β+/β+-thalassemia or β+-thalassemia/Hb E) resulted in a mild clinical symptom whereas two alleles of severe β-thalassemia mutation (βo/βo) produced a severe clinical phenotype. Compound heterozygosity for mild and severe alleles of β-thalassemia (βo/β+-thalassemia or βo-thalassemia/Hb E) led to variable severity of anemia. Coinheritance of α-thalassemia alleviated the severity of β-thalassemia disease in those patients with at least one allele of the mild β-thalassemia genotype. DNA polymorphism at position -158 nt 5´ to the Gγ-globin gene was demonstrated by Xmn I restriction enzyme. Homozygote of the Xmn I site, +/+, was found to have a strong linkage with high Hb F levels and high hemoglobin production in two patients who had mild clinical symptoms. However, some patients who had Xmn I site −/− also had mild clinical symptoms because the Xmn I− was found to be associated with β+-thalassemia mutation.
Conclusion
Types of β-thalassemia mutation and coinheritance of α-thalassemia in the patient who has at least one allele of the mild β-thalassemia genotype are predictive for the clinical severity of the disease. However, a mild clinical symptom in some patients with βo/β+-thalassemia or βo-thalassemia/Hb E who do not have a detectable α-thalassemia haplotype and no linkage with Xmn I++ suggests that there are other confounding factors responsible for the severity differences of the disease.
Heterogeneity in the clinical manifestation of β-thalassemic diseases may occur from the nature of β-globin gene mutations, α-thalassemia gene interaction, or differences in the amount of hemoglobin (Hb) F production. This study was conducted to determine whether these genetic determinant factors can predict phenotypic severity of patients with β-thalassemia and to assess the relationship between the genotype and phenotype of the disease.
Materials and Methods
A total of 144 patients with β-thalassemia were divided into mild (46 patients), intermediate (55 patients), and severe groups (43 patients). DNA analysis based on polymerase chain reaction technique was performed to characterize types of β-thalassemia mutation, interaction of α-thalassemia, and Xmn I polymorphism 5´ to Gγ-globin gene.
Results
Two alleles of mild β-thalassemia mutation (β+/β+-thalassemia or β+-thalassemia/Hb E) resulted in a mild clinical symptom whereas two alleles of severe β-thalassemia mutation (βo/βo) produced a severe clinical phenotype. Compound heterozygosity for mild and severe alleles of β-thalassemia (βo/β+-thalassemia or βo-thalassemia/Hb E) led to variable severity of anemia. Coinheritance of α-thalassemia alleviated the severity of β-thalassemia disease in those patients with at least one allele of the mild β-thalassemia genotype. DNA polymorphism at position -158 nt 5´ to the Gγ-globin gene was demonstrated by Xmn I restriction enzyme. Homozygote of the Xmn I site, +/+, was found to have a strong linkage with high Hb F levels and high hemoglobin production in two patients who had mild clinical symptoms. However, some patients who had Xmn I site −/− also had mild clinical symptoms because the Xmn I− was found to be associated with β+-thalassemia mutation.
Conclusion
Types of β-thalassemia mutation and coinheritance of α-thalassemia in the patient who has at least one allele of the mild β-thalassemia genotype are predictive for the clinical severity of the disease. However, a mild clinical symptom in some patients with βo/β+-thalassemia or βo-thalassemia/Hb E who do not have a detectable α-thalassemia haplotype and no linkage with Xmn I++ suggests that there are other confounding factors responsible for the severity differences of the disease.
ผู้ร่วมงาน
Thalassemia Research Center, Mahidol University
See all items with this value
Institute of Science and Technology for Research and Development, Mahidol University
See all items with this value
Department of Medicine, Siriraj Hospital, Mahidol University
See all items with this value
Hemoglobin Laboratory, Department of Pediatrics, Guangxi University of Medical Sciences, Nanning, Peoples Republic of China.
See all items with this value
ปีที่ผลิตเอกสาร
วันที่บันทึกข้อมูล
2023-05-04
ประเภท
Article
See all items with this value
รูปแบบ
ขนาดหรือจำนวนของเอกสาร
8 pages
ต้นฉบับ/แหล่งที่มาของเอกสาร
Journal of Pediatric Hematology/Oncology ; volume 22, issue 6, page 573-580
ภาษา
รหัส หรือตัวบ่งชี้เอกสาร
ขอบเขต
เจ้าของลิขสิทธิ์
Wolters Kluwer Health, Inc.
See all items with this value
Collections
Tags
New Tags
Position: 220 (18 views)