Study on rare β-globin gene mutations causing β-thalassemia in children

Objective:To study the mutation types, hematological characteristics and clinical features of the rare β-globin gene mutations causing β-thalassemia (β-thal) in children.Methods:Cases tested for thalassemia were selected in the First Affiliated Hospital of Guangxi Medical University from January 2022 to September 2022.Blood routine tests were performed by a blood cell analyzer.Hemoglobin (Hb) analysis was performed by high performance liquid chromatography.Gap polymerase chain reaction (Gap-PCR), fluorescent PCR melting curve and DNA sequencing were used to detect α-thalassemia(α-thal)and β-thal gene mutations.Results:A total of 99 cases of β-thal in children were detected.Among them, two cases were caused by rare β-globin gene mutations leading to β-thal.Case one was a 1-year-old girl with mild anemia, and her blood routine results showed Hb level 101.00 g/L, red blood cell count (RBC)5.43×10¹²/L, mean corpuscular volume(MCV) 56.90 fL, mean corpuscular hemoglobin (MCH) 18.60 pg, mean corpuscular hemoglobin concentration (MCHC)327.00 g/L, hematocrit (HCT) level 0.31 L/L and red blood cell distribution width (RDW) 0.19; Hb analysis showed that Hb A₂ and Hb F were 5.70% and 2.60%, respectively.Gene analysis and DNA sequencing results showed that it was a β-globin gene IVS-Ⅰ-2(T> C) mutant heterozygote.Case two was a 6-year-old boy with mild anemia, and his blood routine results showed Hb level 94.90 g/L, RBC 4.97×10¹²/L, MCV 59.97 fL, MCH 19.11 pg, MCHC 318.70 g/L, HCT level 0.30 L/L and RDW 0.15; Hb analysis showed that Hb A₂ was 5.80%and Hb F was 1.90%.Gene analysis and DNA sequencing results showed that it was a β-globin gene CD95(+A)heterozygous mutation.Conclusion:A heterozygous mutation of β-globin gene CD95(+A) is found to cause β-thal in pediatric patients for the first time in China, which is characterized by mild anemia and increased Hb A₂.The hematological characteristics, Hb analysis and clinical phenotype of β-thal caused by the β-globin gene IVS-Ⅰ-2(T> C) mutant heterozygote are reported in the Chinese pediatric cases for the first time.These two types of βthal gene mutations are rare in China, indicating that they can be easily missed in clinical diagnosis.