Boonyawat Boonchai, Monsereenusorn Chalinee, Traivaree Chanchai
Division of Genetics, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.
Division of Hematology/Oncology, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.
Appl Clin Genet. 2014 Dec 10;7:253-8. doi: 10.2147/TACG.S73058. eCollection 2014.
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.
This study aimed to characterize the spectrum of beta-globin gene mutations in pediatric patients who were followed-up in Phramongkutklao Hospital.
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.
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 beta(E) accounting for 40%.
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.
β地中海贫血是泰国最常见的遗传性疾病之一。临床表型范围从无症状携带者到临床表现各异的病症，包括重型β地中海贫血和中间型β地中海贫血。
本研究旨在对在诗里蒙坤贴医院接受随访的儿科患者中的β珠蛋白基因突变谱进行特征分析。
本研究纳入了80例无亲缘关系的β地中海贫血患者，其中57例为β地中海贫血/血红蛋白E，8例为纯合子β地中海贫血，15例为杂合子β地中海贫血。分别采用多重扩增阻滞突变系统（M-ARMS）、β珠蛋白基因直接DNA测序和缺口聚合酶链反应检测3.4 kb缺失进行突变分析。
在88个等位基因中总共鉴定出13种不同的β地中海贫血突变。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）（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%）通过M-ARMS检测到。通过DNA测序鉴定出六种罕见突变（10.2%），包括密码子35（C>A）占4.5%和起始密码子突变（ATG>AGG）占1.1%，密码子15（G>A）、密码子19（A>G）、密码子27/28（+C）和密码子123/124/125（-ACCCCACC），分别占1.1%。3.4 kb缺失的检出率为4.5%。重型β地中海贫血患者最常见的基因型是密码子⁴¹/⁴²（-TCTT）/密码子26（G>A）或β（E），占40%。
所有β地中海贫血等位基因均通过多种技术进行了特征分析，包括M-ARMS、DNA测序和缺口聚合酶链反应检测3.4 kb缺失。在我们研究的儿科患者中，13种突变占β地中海贫血基因的100%。
