Phenotypic Analysis of the HBA2: C.95 G > A Mutation in China

Hemoglobin. 2024 Sep;48(5):329-332. doi: 10.1080/03630269.2024.2424303. Epub 2024 Nov 5.

Abstract

This study aimed to analyze the clinical phenotype of the HBA2: c.95G>A mutation in the Chinese population and to provide guidance for clinical diagnosis and genetic counseling. Peripheral blood samples were collected from 16 patients, including 6 newborns, 2 children, and 8 adults. Hematological parameters and hemoglobin electrophoresis were analyzed, and genotypes were identified using methods such as PCR combined with reverse dot blot (RDB), nested PCR, gap polymerase chain reaction (Gap-PCR), and DNA sequencing. The results showed that 10 patients had mild anemia, 2 had moderate anemia, and 12 exhibited microcytic hypochromic features with MCV values ranging from 53 to 74.7 fl and MCH values from 16.2 to 25.4 pg. Additionally, 3 cases displayed obvious HbH + HbBarts bands (>15%). Among the 16 cases, various combinations of the HBA2: c.95G>A mutation were observed: one case had -α3.7 combined with HBA2: c.95G>A, another had -α4.2 combined with HBA2: c.95G>A, and five had -SEA combined with HBA2: c.95G>A, while the remaining cases were HBA2: c.95G>A heterozygotes. The study concludes that the HBA2: c.95G>A mutation in the α2 globin gene causes α+ thalassemia. When this mutation is combined with the Southeast Asian deletion (-SEA), it results in HbH disease, characterized by moderate microcytic hypochromic anemia and the presence of HbH + HbBarts bands.

Keywords: DNA sequencing; HBA2; phenotype; α-thalassemia.

MeSH terms

  • Adult
  • Child
  • Child, Preschool
  • China
  • East Asian People / genetics
  • Female
  • Genotype
  • Hemoglobin A2* / genetics
  • Heterozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation*
  • Phenotype
  • alpha-Thalassemia / blood
  • alpha-Thalassemia / diagnosis
  • alpha-Thalassemia / genetics

Substances

  • Hemoglobin A2