Study on the deletion mutation in the promoter region -114 to -102 of ^Aγ-globin gene inducing non-deletional hereditary persistence of fetal hemoglobin

Objective: To study the gene mutation types, hematologic phenotypes and clinical phenotype of the deletion mutations in the promoter region -114 to -102 of ^Aγ-globin gene. Methods: Four cases for thalassemia screening in the First Affiliated Hospital of Guangxi Medical University from March 2022 to December 2023 were selected. Hemoglobin（Hb) analyzer and blood cell analyzer were used to test whole blood samples for Hb analysis and blood routine. The mutations of γ-globin gene promoter region and β-globin gene were detected by Sanger sequencing and fluorescence PCR melting curve analysis. Results: A total of 4 cases with ^Aγ-114 to -102 deletional heterozygotes were detected. The results of Hb analysis showed that fetal hemoglobin (Hb F) levels were 11.2%-37.8% and 2.0%-3.3% for hemoglobin A₂ (Hb A₂). The results of blood routine analysis showed that Hb level was 67 g/L-114 g/L, red blood cell count (RBC) (2.33-4.1)×10¹²/L, mean corpuscular volume (MCV) was 84.02 fL-91.9 fL, and mean corpuscular hemoglobin (MCH) was 27.8 pg-29.7 pg. The genotype analysis for γ-globin gene promoter region and β-globin gene showed that 4 cases were heterozygotes for ^Aγ-114 to -102 deletion, and two of them combined with heterozygotes ^Gγ-158C＞T gene mutation. All 4 cases had β-globin gene mutations. Their genotypes were as follows: heterozygous mutation of Codon 41-42 (-TTCT), homozygous mutation of Codon 41-42 (-TTCT), compound mutation of IVS-Ⅱ-654 (C＞T) and Codon 41-42 (-TTCT), and compound mutation of Codon17 (A＞T) and Codon 71-72 (+A). Conclusion: ^Aγ-114 to -102 deletional heterozygote and coinherited β-thalassemia are first identified in Chinese population, presenting with mild or moderate clinical manifestations. ^Aγ-114 to -102 deletional mutation causes non-deletional hereditary persistence of fetal hemoglobin (nd-HPFH), and it can reduce the clinical severity in patients with β-thalassemia.