Analysis of deletional hereditary persistence of fetal hemoglobin/δβ‐thalassemia and δ‐globin gene mutations in Southerwestern China

Abstract

Background Deletional hereditary persistence of fetal hemoglobin (HPFH)/δβ‐thalassemia and δ‐thalassemia are rare inherited disorders which may complicate the diagnosis of β‐thalassemia. The aim of this study was to reveal the frequency of these two disorders in Southwestern China. Methods A total of 33,596 subjects were enrolled for deletional HPFH/δβ‐thalassemia, and positive individuals with high fetal hemoglobin (Hb F) level were diagnosed by multiplex ligation‐dependent probe amplification (MLPA). A total of 17,834 subjects were analyzed for mutations in the δ‐globin gene. Positive samples with low Hb A2 levels were confirmed by δ‐globin gene sequencing. Furthermore, the pathogenicity and construction of a selected δ‐globin mutation were analyzed. Results A total of 92 suspected cases with Hb F ≥5.0% were further characterized by MLPA. Eight different deletional HPFH/δβ‐thalassemia were observed at a frequency of 0.024%. In addition, 195 cases suspected to have a δ‐globin gene mutation (Hb A2 ≤2.0%) were characterized by molecular analysis. δ‐Globin gene mutation was found at a frequency of 0.49% in Yunnan. The pathogenicity and construction for a selected δ‐globin mutation was predicted. Conclusion Screening of these two disorders was analyzed in Southwestern China, which could define the molecular basis of these conditions in this population.

Molecular epidemiology and hematologic characterization of δβ-thalassemia and hereditary persistence of fetal hemoglobin in 125,661 families of greater Guangzhou area, the metropolis of southern China

“…To date, the Taiwanese deletion has only been reported as the case study , [18,19]. Compared to the three types, that is, Chinese G γ ( A γδβ) 0 -thal, SEA-HPFH and A γ-196 C-T mutation [9,10,20], the individual with the Taiwanese deletion showed higher HbA2 levels than 6% of our study cohort. This higher HbA2 level may due to deletion of the βglobin gene promoter.…”

“…Chinese G γ ( A γδβ) 0 thalassemia and SEA-HPFH are the most common deletional (δβ) 0 -thal/HPFH disorders in this region. The prevalence of these two disorders was lower than that in the Chinese Zhuang population but higher than that in the Chinese Hakka and Yunnan populations [9][10][11]. These differences may be caused by the population composition, which is rather homogeneous in those regions.…”

“…Table 1 lists those two β-globin cluster deletions and their associated phenotypes in southern China. The prevalence of deletional HPFH/δβ-thalassemia was reported in Yunnan, Guangdong and Guangxi provinces [9,10]. This prevalence was highest in the Guangxi Zhuang Autonomous Region, reaching 0.21%, while it was lower than 0.002% in Hakka People living in the Guangdong Meizhou areas [11].…”

Molecular Epidemiology and Hematologic Characterizationof δβ-thalassemia and Hereditary Persistence of Fetal Hemoglobin in 125661 Families of Greater Guangzhou Area, the metropolis of Southern China

“…To date, the Taiwanese deletion has only been reported as the case study , [18,19]. Compared to the three types, that is, Chinese G γ( A γδβ) 0 -thal, SEA-HPFH and A γ-196 C-T mutation [9,10,20], the individual with the Taiwanese deletion showed higher HbA2 levels than 6% of our study cohort. This higher HbA2 level may due to deletion of the β-globin gene promoter.…”

“…Table 1 lists those two β-globin cluster deletions and their associated phenotypes in southern China. The prevalence of deletional HPFH/δβthalassemia was reported in Yunnan, Guangdong and Guangxi provinces [9,10]. This prevalence was highest in the Guangxi Zhuang Autonomous Region, reaching 0.21%, while it was lower than 0.002% in Hakka People living in the Guangdong Meizhou areas [11].…”