Unusual β-Globin Haplotype Distribution in Newborns from Bengo, Angola

Abstract

Mutations on the HBB gene are a common cause of hemoglobinopathies, including sickle cell anemia, a severe genetic condition that constitutes a major public health concern. The aim of this study was to determine the prevalence of sickle cell anemia and β-globin haplotype distribution in newborns from the Bengo region. The first two exons of β-globin gene were sequenced, and the variability at the single nucleotide polymorphism (SNP) defining the Hb S (HBB: c.20A>T) haplotypes, was analyzed by a SNaPshot^® Multiplex system. About 3.3% of the children were homozygous for Hb S, and 82.2% had as background the Bantu/Central African Republic (BAN/CAR) haplotype, 11.2% the Benin (BEN) and 6.6% the Senegal (SEN). The estimate of Hb S reached the very high value of 0.1476 ± 0.0133, with the aggravating factor of 82.2% of the sickle alleles being anchored in the BAN/CAR haplotype, associated with the more severe sickle cell anemia phenotypes. Also, the high prevalence of the SEN haplotype was not expected, having therapeutic consequences since is associated with more severe outcomes. In addition, two β-thalassemia (β-thal) variants were also detected, IVS I-110 (G>A) (HBB: c.93-21G>A) and codon 39 (C>T) (HBB: c.118C>T), together totaling a frequency of 1.3%. Some of the newborns with these mutations were compound heterozygotes for Hb S, likely carrying genotypes consistent with sickle cell disease. As a whole, infants molecularly diagnosed with sickle cell disease accounted for 4.5% of newborns from Bengo, Angola, a figure that per se, highlights the urgent need of implementing policies warranting surveillance of these children, in parallel with community education in the region.

Keywords:

• Bengo
• Angola
• β-globin gene
• newborn screening
• sickle cell disorders

Acknowledgments

The authors wish to acknowledge all the researchers and technicians who supported this study, especially from CISA, Bengo, Angola, and the Hospital Geral do Bengo, namely nurses from CISA and from maternity. In particular, the authors wish to express their gratitude to Inês de Deus (CISA). We wish to express our gratitude to all mothers who allowed the realization of this study by authorizing the sample collection. Author contribution: C. Tchonhi, A. Amorim, M.J. Prata and M. Brito participated in the study design, study implementation, training and supervision of the laboratory and field staff; E. Borges, C. Tchonhi, C.S.B. Couto, V. Gomes, A. Amorim, M.J. Prata and M. Brito participate in laboratory analysis, data collection, statistical analysis and interpretation; E. Borges and M.J. Prata wrote the first draft of the manuscript. All authors revised the manuscript and approved its final version.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was funded by the promoters of Health Research Center of Angola (CISA) namely Camões, Institute of Cooperation and Language, Portugal; Calouste Gulbenkian Foundation, Portugal; Government of Bengo Province; Angolan Ministry of Health; FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the COMPETE 2020 (Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020; and by Portuguese funds through FCT (Fundação para a Ciência e a Tecnologia), in the framework of the project POCI-01-0145-FEDER-007274 to i3S.