Clinical and Genetic Pattern of β-Thalassemia Major in East Java, Indonesia

Background: Beta thalassemia major is the most common monogenic mutation disorder in Indonesia, with steadily increasing frequency. However, there are limited studies regarding genetic distribution and its relationship with the patient’s clinical manifestation. This study aimed to identify the genetic mutation frequency and its association with the clinical phenotype pattern among β-thalassemia major patients in East Java, Indonesia. Methods: In this observational study, we include subjects who have diagnosed with β-thalassemia previously through Hb electrophoresis. Demographic distribution with several ethnicities of Javanese, Sundanese, Chinese, Maduranese, and Batak was recorded. From each subject, a total of 6 mL of blood sample was collected and divided into two ethylene diamine tetraacetic acid (EDTA) tubes for CBC and DNA extraction. DNA samples were analyzed by PCR and followed by Sanger sequencing. Results: A total of 91 subjects were included in this study, with a median age of 22.25 ± 7.56 years old; consisting of 52 females and 39 males, with Javanese as the most common ethnicity. There are 22 types of mutation were identified through Sanger sequencing. The most common mutation was IVS-1-5/CD 26 and the CD 35/CD 26 observed in 36 (39.5%) and 19 (20.8%), respectively. While 9 subjects (9.8%) had no mutation detected. Several clinical phenotypes, including iron overload, short stature, severe anemia, and splenomegaly, were most prevalent among the two most common genetic mutations. Conclusion: There is variability in clinical phenotype in β-thalassemia observed in several types of genotype mutations. Among all the mutations found in East Java, the genotypes IVS-1-5/CD 26 and CD 35/CD 26 were the two most frequent genotypes. Those genotypes are linear with the severity of the phenotype in β-thalassemia, such as severe anemia, iron overload, short stature, and splenomegaly.