Rare IVSⅠ-2 (T＞A) mutation in the β-globin gene causing β-thalassemia: a case report

Objective To investigate the hematological parameters and clinical phenotypes of a heterozygote carrying the rare IVSⅠ-2 (T＞A) mutation in the β-globin gene.

Methods Patients suspected of having β-thalassemia who underwent initial screening via routine blood tests red blood cell count (RBC), hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), hematocrit (HCT), red blood cell distribution width (RDW), and analyses of hemoglobin A₂ (Hb A₂) and fetal hemoglobin (Hb F) were enrolled in this study. Common β-thalassemia gene mutations were detected using fluorescent polymerase chain reaction (PCR) melting curve analysis. For individuals in whom no mutations were identified by the above methods, DNA sequencing was further performed to detect rare or unknown β-thalassemia gene mutations.

Results Among 235 patients with β-thalassemia, 1 patient with rare β-thalassemia was identified. The patient harbored a heterozygous IVSⅠ-2 (T＞A) (HBB:c.92+2 T＞A) mutation in the β-globin gene coexisting with α-thalassemia of the αα/-α^3.7 deletion type. The patient's routine blood test results were as follows: RBC 5.89×10¹²/L, Hb 107.00 g/L, MCV 55.40 fL, MCH 18.15 pg, MCHC 327.70 g/L, HCT 0.327 and RDW 0.18. The hemoglobin analysis results of the patient revealed an Hb A₂ level of 5.0% and an Hb F level of 4.0%.

Conclusion β-Thalassemia caused by the rare heterozygous IVS Ⅰ-2 (T＞A) mutation in the β-globin gene is reported for the first time in China. Clinically, the patient presents with mild anemia, decreased MCV and MCH levels, and elevated Hb A₂. This mutation is relatively rare and prone to missed diagnosis.