ORIGINAL RESEARCH article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1622391
This article is part of the Research TopicInsights in Genetics of Common and Rare Diseases 2024View all 26 articles
The rare hemoglobin variants Hb O-Arab and Hb D-Punjab identified in population-based genetic screening throughout Guangxi, China
Provisionally accepted
Chunrong Gui1Zifeng Cheng2Yongsheng Chen3Yunting Ma2Hongfei Chen2Wei Wei1
Xianda Wei1Juliang Liu1
Xu Zhou2Qianqian Du4Yinghui Lai3*
Baoheng Gui1*- 1Center for Medical Genetics and Genomics, the Second Affiliated Hospital of Guangxi Medical University, Nanning, China
- 2The Second School of Medicine, Guangxi Medical University, Nanning, China
- 3Department of Hematology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
- 4Berry Genomics Corporation, Beijing, China
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Background: Hemoglobinopathies are a group of autosomal recessive disorders characterized by a high degree of clinical and genetic heterogeneity. Comprehensive genetic screening for hemoglobin variants is crucial for prevention and treatment of these conditions. Single-molecule real-time (SMRT) sequencing enables efficient and reliable analysis of common and complex or rare hemoglobin variants.We launched a population-based genetic screening program for hemoglobinopathies in Guangxi, China, using SMRT. The in silico structural predictions based on Alphafold2 were performed for the rare variants identified. Additionally, a comprehensive literature review was conducted to elucidate the origin and genotype-phenotype correlation of these variants.: A total of 11019 participants throughout Guangxi were recruited via the screening program. In two unrelated families, the variants, Hb O-Arab and Hb D-Punjab at the same genetic locus, were identified with an extremely low frequency of 0.0045% [1/(11019*2), respectively] in the population. Structural prediction showed Hb O-Arab exerted a relatively significant impact on the hemoglobin structure, whereas the influence of Hb D-Punjab was minimal. This was consistent with findings from the literature review and the two recruited families, which confirmed that individuals with Hb O-Arab presented relatively obvious manifestations compared to those with Hb D-Punjab. Conclusions: Two rare variants, Hb O-Arab and Hb D-Punjab, were identified in Guangxi, China using SMRT. The first report of Hb O-Arab enriches the spectrum of hemoglobin variants in the Chinese population. Analyzing the frequency, origin and genotype-phenotype correlation of these variants could pave the way for clinical management and genetic counseling for hemoglobinopathies.
Keywords: Hb O-Arab, Hb D-Punjab, hemoglobinopathy, genetic screening, Chinese population, single-molecule real-time sequencing, genotype-phenotype correlation
Received: 03 May 2025; Accepted: 30 Jul 2025.
Copyright: © 2025 Gui, Cheng, Chen, Ma, Chen, Wei, Wei, Liu, Zhou, Du, Lai and Gui. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yinghui Lai, Department of Hematology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
Baoheng Gui, Center for Medical Genetics and Genomics, the Second Affiliated Hospital of Guangxi Medical University, Nanning, China
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