Abstract
BackgroundIndividuals with δβ-thalassemia/HPFH and β-thalassemia usually present with intermedia or thalassemia major. No large-scale survey on HPFH/δβ-thalassemia in southern China has been reported to date. The purpose of this study was to examine the molecular epidemiology and hematologic characteristics of these disorders in Guangzhou, the largest city in Southern China, to offer advice for thalassemia screening programs and genetic counseling.MethodsA total of 125,661 couples participated in pregestational thalassemia screening. 654 subjects with fetal hemoglobin (HbF) level ≥ 5% were selected for further investigation. Gap-PCR combined with Multiplex ligation dependent probe amplification (MLPA) was used to screen for β-globin gene cluster deletions. Gene sequencing for the promoter region of HBG1 /HBG2 gene was performed for all those subjects.ResultsA total of 654 individuals had hemoglobin (HbF) levels≥5, and 0.12% of the couples were found to be heterozygous for HPFH/δβ-thalassemia, including Chinese Gγ (Aγδβ)0-thal, Southeast Asia HPFH (SEA-HPFH), Taiwanese deletion and Hb Lepore–Boston–Washington. The highest prevalence was observed in the Huadu district and the lowest in the Nansha district. Three cases were identified as carrying β-globin gene cluster deletions, which had not been previously reported. Two at-risk couples (0.0015%) were required to receive prenatal diagnosis. We also found 55cases of nondeletional-HPFH (nd-HPFH), including 54 with Italian nd-HPFH and one with the Aγ-197C-T heterozygous state. It is difficult to discriminate between Chinese Gγ (Aγδβ)0-thal and Italian nd-HPFH carriers using hemoglobin (Hb) analysis.ConclusionsThis study is the first to describe the familial prevalence of HPFH/δβ-thalassemia and the high-risk rate in Greater Guangzhou Area, and the findings will support the implementation of thalassemia screening for three common deletions by gap-PCR. We also presented a systematic description of genotype-phenotype relationships which will be useful for genetic counseling and prenatal diagnostic services for β-thalassemia intermedia.
Highlights
Individuals with δβ-thalassemia/hereditary persistence of fetal hemoglobin (HPFH) and β-thalassemia usually present with intermedia or thalassemia major
This study is the first to describe the familial prevalence of HPFH/δβ-thalassemia and the high-risk rate in Greater Guangzhou Area, and the findings will support the implementation of thalassemia screening for three common deletions by gap-PCR
We presented a systematic description of genotype-phenotype relationships which will be useful for genetic counseling and prenatal diagnostic services for β-thalassemia intermedia
Summary
Individuals with δβ-thalassemia/HPFH and β-thalassemia usually present with intermedia or thalassemia major. No large-scale survey on HPFH/δβ-thalassemia in southern China has been reported to date. Thalassemias include α-, β-, delta-beta-thalassemia (δβthalassemia) and hereditary persistence of fetal hemoglobin (HPFH),as determined by the type of globin chain that is involved [1]. HPFH (OMIM #141749, ORPHA:46532) includes deletional HPFH and nondeletional HPFH (nd-HPFH), and the former is caused by large deletions in the region between the γ- and β-globin genes [3]. More than 50 HPFH/δβthalassemia deletions have been reported to date, which are related to different ethnic backgrounds 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]. All these variants were found in different areas, such as Hb Lepore-Hollandia (HGVS: NG_ 000007.3: g.63290_70702del), which has been reported in people of southern and southeast Asia, with rare occurrences being observed in Europe [12]
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