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Chanchai Traivaree,1 Chalinee Monsereenusorn,1 Piya Rujkijyanont,1 Warakorn Prasertsin,2 Boonchai Boonyawat3 1Division of Hematology/Oncology, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand; 2Department of Pediatrics, Queen Savang Vadhana Memorial Hospital, Chonburi, Thailand; 3Division of Genetics, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand Introduction: Beta-thalassemia is a group of inherited hemolytic anemias and one of the most common genetic disorders in Thailand. The clinical spectrum of beta-thalassemia disease ranges from mild to severe clinical symptoms including mild beta-thalassemia intermedia (TI) and severe beta-thalassemia major (TM). Objective: This study aimed to determine the correlation between beta-globin gene (HBB) mutations and their phenotypic manifestations by evaluating patients’ clinical characteristics, transfusion requirements, growth and hematologic parameters, and hemoglobin typing among pediatric patients treated at Phramongkutklao Hospital. Materials and methods: Seventy beta-thalassemia patients, including 63 with beta-thalassemia/hemoglobin E (HbE) and 7 with either homozygous or compound heterozygous beta-thalassemia, were enrolled in this study. Their clinical presentation, growth parameters and laboratory findings were reviewed and analyzed. The mean follow-up time was 10.52±5.62 years. Mutation analysis in each individual was performed using multiplex amplification refractory mutation system (M-ARMS), direct DNA sequencing of beta-globin gene and gap PCR for 3.4 kb deletion detection. Results: All 7 homozygous and compound heterozygous beta-thalassemia patients were classified in TM. Among 63 patients with beta-thalassemia/HbE, 58 were classified in TM and 4 were classified in TI. Mean age at diagnosis was 0.8±0.49 years for homozygous or compound heterozygous beta-thalassemia and 3.43±3.5 years for beta-thalassemia/HbE. The most common HBB mutation was HBB:c.126_129delCTTT [codon 41/42 (-TCTT)] found in 34 alleles (48.6%). The height for age was also lower in homozygous beta-thalassemia patients (

Chanchai Traivaree,1 Chalinee Monsereenusorn,1 Arunotai Meekaewkunchorn,2 Premsak Laoyookhong,3 Saranya Suwansingh,4 Boonchai Boonyawat5 1Division of Hematology/Oncology, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, 2Division of Hematology/Oncology, Department of Pediatrics, 3Division of Neonatology, Department of Pediatrics, Queen Sirikit National Institute of Child Health, Bangkok, 4Division of Hematology/Oncology, Department of Pediatrics, Chiangrai Prachanukroh Hospital, Chiang Rai, 5Division of Genetics, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand Abstract: Congenital factor VII (FVII) deficiency is a rare inherited coagulopathy. The clinical manifestations and clinical findings vary widely, ranging from asymptomatic to life-threatening bleeding, including intracranial hemorrhage (ICH), with prolonged prothrombin time, normal partial thromboplastin time and normal platelet counts, which are confirmed by the low level of FVII assay. Treatment consists of fresh frozen plasma (FFP), prothrombin complex concentrates (PCCs), and recombinant activated FVII to treat bleeding and prophylactic therapy. Here, we report four patients with FVII levels T was the most common (50%) mutation identified in our study, followed by the K376X nonsense mutation (37.5%). In our study, we found that genetic information affected the severity of congenital FVII deficiency with ICH. Keywords: mutation analysis, factor VII deficiency, Thai children

Boonchai Boonyawat,1 Chalinee Monsereenusorn,2 Chanchai Traivaree2 1Division of Genetics, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand; 2Division of Hematology/Oncology, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand 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. Keywords: mutation analysis, beta-globin gene, Thai children