Compound Heterozygosity for Hb Queens Park (α32(B13)Met→Lys) and α-thalassemia Found in Northern Thailand
摘要
Hb Queens Park [QP; α32(B13)Met→Lys,(HBA1:c.98T > A)] is a rare α-globin variant. Its genotype-phenotype relationship with α-thalassemia has not been described in Northern Thailand. Hemoglobin analysis was performed using capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC). The α0-thalassemia (--SEA, --Thai, and --Chiang Rai) was diagnosed by real-time PCR with high-resolution melting analysis, whereas the α+-thalassemia (-α3.7 and -α4.2) was identified by conventional gap-PCR. Next-generation sequencing (NGS) was used to identify the mutations in the HBA1, HBA2, and HBB genes. Three individuals with Hb QP were studied. A heterozygosity for Hb QP alone displayed normal red cell indices, revealing minor hematological effects. The individual with compound heterozygosity for Hb QP and α+-thalassemia -α3.7 deletion who coinherited with HbE trait showed mild anemia alongside persistent microcytosis and HbA2/E levels lower than 25%. A subject with compound heterozygosity for Hb QP and α0-thalassemia --SEA deletion displayed significant microcytosis and moderate anemia, demonstrating a more severe phenotype. Hb QP alone typically shows mild or no symptoms but exhibits increased hematological severity when combined with α-thalassemia. This information might be useful for thalassemia screening, genetic counseling, control, prevention, and treatment.