Association of Hb Shenyang [α26(B7)Ala→Glu, GCG>GAG,HBA2: c.80C>A (orHBA1)] with Several Types of α-Thalassemia in Thailand

Hb Shenyang [alpha 26(B7)Ala -> Glu,HBA2: c.80C>A (orHBA1)] is a rare alpha chain variant. Its genotype-phenotype relationship and origin have not been described in Thailand before. Three Thai subjects (P1-P3) carrying this variant were studied. Hemoglobin (Hb) analysis was performed by capillary electrophoresis (CE) and high performance liquid chromatography (HPLC) as well as molecular characterization using appropriate polymerase chain reaction (PCR) techniques and DNA sequencing. Hemoglobin analysis by HPLC revealed fast-moving abnormal peaks at a retention time (RT) of 1.59-1.62 min., while CE revealed a fast-moving abnormal Hb at zone 12 and ahead of Hb A(2)in three subjects. DNA analysis revealed a C>A transition at codon 26 of the alpha 2-globin gene glutamic acid to replace alanine, corresponding to Hb Shenyang. The Southeast Asian [- -(SEA)alpha-thalassemia-1 (alpha-thal-1)] deletion was also identified in P1 and his mother, while Hb Constant Spring (Hb CS,HBA2: c.427T > C) was identified in P2. The Hb Shenyang concentration measured by CE revealed 5.1-17.2% heterozygosity with normal red blood cell (RBC) parameters. The alpha haplotype [+ - S + - + -] [S signifies the inter zeta hypervariable region (HVR)] was associated with the Thai Hb Shenyang. The genotype-phenotype relationship indicates Hb Shenyang is likely a non pathological Hb variant that has neither dramatic clinical symptoms nor hematological anomalies. A simple multiplex allele-specific PCR for rapid diagnosis of Hb Shenyang has been developed.