Diagnosis and Prenatal Diagnosis in a Chinese Family Carrying the Rare α-Thalassemia Gene HBA2: c.1A>G Mutation

Abstract

The aim of this study was to identify the rare thalassemia genotype in a family and perform prenatal diagnosis (PND) on the proband’s unborn child. Peripheral blood was collected from the family members for hematology analysis and capillary electrophoresis (CE) analysis. Peripheral blood and cord blood were analyzed by gap-polymerase chain reaction (gap-PCR), reverse dot-blot and Sanger sequencing for genotypes of α-thalassemia (α-thal). A heterozygous mutation, HBA2: c.1A>G, was identified in the proband and his father. Two compound heterozygous variants, HBA2: c.1A>G and the – –^SEA (Southeast Asian) deletion, were revealed in the proband’s unborn child. The hemoglobin (Hb) CE result of the fetal cord blood indicated the fetus had Hb H disease. We have identified a rare thalassemia mutation (HBA2: c.1A>G) in a Chinese family and enriched the rare α-thal gene pool in the Chinese population. When the patient’s phenotype does not match the genotype detected by thalassemia gene detection kits, further investigation of rare genotypes should be conducted to avoid missed diagnosis or misdiagnosis, which can help guide clinical diagnosis, population screening and genetic counseling.

Keywords:

• α-Thalassemia (α-thal)
• HBA2: c.1A>G mutation
• family pedigree
• analysis
• People’s Republic of China (PRC)

Acknowledgments

We are grateful to our current laboratory members for their helpful comments on the manuscript.

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 supported by the National Natural Science Foundation of China [Grant No. 81360091] and Health Department Research Fund of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China [Grant No. Z20170528].