Molecular and hematological characterization of hemoglobin Hope/hemoglobin E and hemoglobin Hope/alpha-thalassemia 2 in Thai patients.
We report the hematological and molecular characterization of compound heterozygosity for hemoglobin (Hb) Hope/Hb E and double heterozygosity for Hb Hope/ alpha-thalassemia 2 found in 2 unrelated Thai individuals. The first proband presented with slight anemia and mild hypochromic microcytosis. Routine cellulose acetate Hb electrophoresis at pH 8.6 revealed in addition to Hb E another variant migrating slightly more anodic to Hb A. On cation exchange high-pressure liquid chromatography, the variant was eluted in the amount of 60.9% after Hb E The same abnormal Hb was found in a second family in which the proband and her younger sister were both double heterozygotes for this Hb variant and deletional alpha-thalassemia 2, whereas an older sister was a pure carrier of the variant. The amounts of this variant were found to be 34.9%, 35.4%, and 38.3% in the proband, her younger sister, and her older sister, respectively. Direct DNA sequencing of the amplified beta-globin genes of both probands identified the GGT (Gly)-GAT (Asp) mutation at codon 136 corresponding to Hb Hope. beta-Globin gene haplotype analysis demonstrated that all the Thai betaHope genes were associated with the same haplotype, (+ - - - - + +), indicating a single origin of this variant in Thailand. A simple method based on allele-specific polymerase chain reaction for accurate diagnosis of the Hb Hope is described.
Chunpanich
Sunisa
S
Graduate School, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen Thailand.
Fucharoen
Supan
S
Sanchaisuriya
Kanokwan
K
Fucharoen
Goonnapa
G
Kam-itsara
Kasian
K
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D004586:Electrophoresis; D005192:Family Health; D005260:Female; D006239:Haplotypes; D006446:Hemoglobin E / Q000235:genetics*; D006453:Hemoglobinopathies / Q000175:diagnosis*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D020125:Mutation, Missense; D010375:Pedigree; D011247:Pregnancy; D013785:Thailand; D017085:alpha-Thalassemia / Q000235:genetics*
D006455:Hemoglobins, Abnormal; D006446:Hemoglobin E; C038623:hemoglobin Hope