Molecular analysis of beta-globin gene mutations among Thai beta-thalassemia children: results from a single center study
Molecular analysis of beta-globin gene mutations among Thai beta-thalassemia children: results from a single center study
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DOI：
10.2147/tacg.s73058
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发表时间：
2014-01-01
影响因子：
3.1
通讯作者：
Traivaree, Chanchai
中科院分区：
文献类型：
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作者：
Boonyawat, Boonchai;Monsereenusorn, Chalinee;Traivaree, Chanchai
背景：β-地中海贫血是泰国最常见的遗传性疾病之一。临床表型的范围从沉默的载体临床表现的条件，包括严重的β地中海贫血重型和轻度β地中海贫血intermedia.Objective：这项研究的目的是表征谱的β-珠蛋白基因突变的儿科患者谁是后续在Phramongkutklao医院。80名不相关的β-地中海贫血患者入组本研究，包括57名β-地中海贫血/血红蛋白E患者，8名纯合子β-地中海贫血患者，15例为杂合子β地中海贫血。结果：在88个等位基因中，共检测出13种不同的β-地中海贫血突变，突变类型分别为多重扩增难治突变系统（M-ARMS）、β-珠蛋白基因直接测序和缺口聚合酶链反应（gap PCR）。最常见的突变是密码子41/42（-TCTT）（37.5%），其次是密码子17（A>T）（26.1%）、IVS-I-5（G>C）（8%）、IVS-II-654（C>T）M-ARMS检测到IVS-I-1（G>T）（6.8%）、IVS-I-1（G>T）（4.5%）和密码子71/72（+ A）（2.3%）这六种常见突变（85.2%）。DNA测序发现6个不常见突变（10.2%），其中35号密码子（C>A）4.5%;起始密码子（ATG>AGG）1.1%; A）、密码子19（A>G）、密码子27/28（+ C）和密码子123/124/125（-ACCCCACC）。检测到3.4kb的缺失，占4.5%。结论：M-ARMS、DNA测序和缺口聚合酶链反应等技术可检测出重型β地中海贫血患者的所有等位基因，其基因型以密码子41/42（-TCTT）/密码子26（G>A）或β E为主，占40%。13个突变占100%的β-地中海贫血基因的儿科患者在我们的研究。
Background: Beta-thalassemia is one of the most common genetic disorders in Thailand. Clinical phenotype ranges from silent carrier to clinically manifested conditions including severe beta-thalassemia major and mild beta-thalassemia intermedia.Objective: This study aimed to characterize the spectrum of beta-globin gene mutations in pediatric patients who were followed-up in Phramongkutklao Hospital.Patients and methods: Eighty unrelated beta-thalassemia patients were enrolled in this study including 57 with beta-thalassemia/hemoglobin E, eight with homozygous beta-thalassemia, and 15 with heterozygous beta-thalassemia. Mutation analysis was performed by multiplex amplification refractory mutation system (M-ARMS), direct DNA sequencing of beta-globin gene, and gap polymerase chain reaction for 3.4 kb deletion detection, respectively.Results: A total of 13 different beta-thalassemia mutations were identified among 88 alleles. The most common mutation was codon 41/42 (-TCTT) (37.5%), followed by codon 17 (A>T) (26.1%), IVS-I-5 (G>C) (8%), IVS-II-654 (C>T) (6.8%), IVS-I-1 (G>T) (4.5%), and codon 71/72 (+ A) (2.3%), and all these six common mutations (85.2%) were detected by M-ARMS. Six uncommon mutations (10.2%) were identified by DNA sequencing including 4.5% for codon 35 (C>A) and 1.1% initiation codon mutation (ATG>AGG), codon 15 (G. A), codon 19 (A>G), codon 27/28 (+ C), and codon 123/124/125 (-ACCCCACC), respectively. The 3.4 kb deletion was detected at 4.5%. The most common genotype of beta-thalassemia major patients was codon 41/42 (-TCTT)/codon 26 (G>A) or betaE accounting for 40%.Conclusion: All of the beta-thalassemia alleles have been characterized by a combination of techniques including M-ARMS, DNA sequencing, and gap polymerase chain reaction for 3.4 kb deletion detection. Thirteen mutations account for 100% of the beta-thalassemia genes among the pediatric patients in our study.