RESUMO
The types of ß-thalassemia mutations, α-thalassemia interactions, and Hb F-associated SNPs have been described in association with variable disease phenotypes. This study aimed to determine the updated spectrum of ß-thalassemia mutations and evaluate the contribution of primary and secondary genetic modifiers and SNPs to disease severity, age at onset, and predicted life expectancy in southern Thai ß-thalassemia patients. A total of 181 ß-thalassemia patients were enrolled and 135 ß0-thalassemia/Hb E patients without α-thalassemia interactions were divided into three categories according to disease severity, age at onset, and predicted life expectancy. A total of 16 ß-thalassemia mutations were identified in this study, and the three most common ß-thalassemia mutations accounted for 61.4% of all mutations. It was also found that the XmnI polymorphism and rs2071348 were associated with age at onset and the predicted life expectancy. More than 82% of ß0-thalassemia/Hb E patients with CC genotype (XmnI) were 3 years old or younger at onset. Additionally, >90% of the higher predicted life expectancy in ß0-thalassemia/Hb E patients had the T allele of XmnI. Therefore, genetic prediction for age at onset and life expectancy is beneficial and practical during prenatal diagnosis or newborn screening for better genetic counseling and optimal management.
RESUMO
This study reports the case of 2-year-old Northeastern Thai girl with ß-thalassemia (ß-thal) disease who has required regular blood transfusions since she was 8 months old. Hemoglobin (Hb) analysis by high performance liquid chromatography (HPLC) separated Hb A2/E (16.5%), Hb F (22.7%), Hb A (51.8%) and an abnormal peak (Hb X) found at a retention time (RT) of 5.05 min. (C-window) with 2.8%. Multiplex gap-polymerase chain reaction (gap-PCR) revealed heterozygous α-thalassemia-2 (α-thal-2) (-α3.7/αα; NG_000006.1: g.34164_37967 del3804). This patient was suspected of having a ß-globin chain variant and Hb E (HBB: c.79G>A) according to the high Hb F level and disease presentations. Surprisingly, Hb Mahasarakham (the geographic origin of the proband), a novel single nucleotide deletion (-G) at the first nucleotide of codon 121 (HBB: c.364delG), was identified by direct DNA sequencing and secondary confirmation by PCR-restriction fragment length polymorphism (PCR-RFLP). This novel mutation causes a frameshift mutation and added 10 more residues to the ß-globin chain that was elongated to 156 amino acids. Molecular basis of this novel mutation in the heterozygous state is required to confirm the mode of inheritance.
