Genetic research and clinical analysis of β‐globin gene cluster deletions in the Chinese population of Fujian province: A 14‐year single‐center experience

Background Heterozygotes of HPFH and δβ thalassemia are clinically asymptomatic or have mild hemoglobin (Hb) values. However, when both HPFH and δβ‐thalassemia are coinherited with heterozygous β‐thalassemia, patients may progress to a clinical phenotype of thalassemia intermedia or thalassemia major. The purpose of this study was to characterize the genotypes and analyze the phenotypes of these disorders in Fujian Province, to offer advice for genetic counseling and accurate prenatal diagnosis in this region. A total of 55 001 subjects were participated in thalassemia screening. 142 subjects with HbF levels ≥10%, before the blood transfusion, were selected for further investigation. Methods Multiplex ligation‐dependent probe amplification (MLPA) and Gap‐PCR were used to screen for three β‐globin gene cluster deletions: Chinese G γ( A γδβ) 0 thalassemia and Southeast Asia HPFH (SEA‐HPFH) deletion and 1357 bp deletion (NG‐7.3:g.69997‐71353 del 1357). Results A total of 142 patients with HbF (≥10%) were enrolled to characterize the molecular basis of β‐globin gene cluster deletions in our study; 22 cases 0.04% (22/55 001) were definitively diagnosed with β‐globin gene cluster deletions. Ten cases were heterozygous for the Chinese G γ( A γδβ) 0 ‐thal mutations, 10 cases were heterozygous for SEA‐HPFH, and one case was compound heterozygous for SEA‐HPFH and the α‐thal mutation. The 1357 bp deletion (NG‐7.3:g.69997‐71353 del 1357) was detected in one case. Moreover, the hemoglobin A 2  levels in patients who were heterozygous for Chinese G γ( A γδβ) 0 ‐thal were statistically lower than in cases with SEA‐HPFH deletion( p  < 0.05). Conclusion In Fujian Province, the prevalence of common β‐globin gene cluster deletions was 0.04%. What's more, the most common β‐globin cluster deletions are the Chinese G γ( A γδβ) 0 and SEA‐HPFH.