Complex interaction of Hb E [beta26(B8)Glu-->Lys], Hb Korle-Bu [beta73(E17)Asp-->Asn] and a deletional alpha-thalassemia-1 in pregnancy.
A pregnant Thai woman with mild hypochromic microcytic anemia caused by alpha- and beta- globin defects is described. The proband was a 26-year-old pregnant woman discovered through our ongoing thalassemia screening program. Initial hemoglobin (Hb) high performance liquid chromatography (HPLC) analysis revealed a homozygosity for an unknown variant at the D window, inconsistent with results of family analyses. Further Hb analysis using automated capillary zone electrophoresis identified that the proband was in fact a compound heterozygote for Hb E [beta26(B8)Glu-->Lys, GAG>AAG] and another beta chain variant. DNA analysis demonstrated that she carried the Hb Korle-Bu mutation [beta73(E17)Asp-->Asn (GAT>AAT)] in trans to the Hb E and an alpha-thalassemia-1 (alpha-thal-1) with the Southeast Asian (- -(SEA)) deletion. Family studies identified that her father and sister were double heterozygotes for Hb Korle-Bu and alpha-thal-1, whereas her mother was a double heterozygote for Hb E/Hb Constant Spring [Hb CS; alpha142, Term-->Gln (TAA>CAA in alpha2)]. The genotype-phenotype relationship observed in this Thai family with complex hemoglobinopathies and methods for characterization are presented.
Siriratmanawong
Nirut
N
Health Promoting Centre Region 8, Nakhonsawan, Ministry of Public Health, Nakornsawan, Thailand.
Chansri
Wichuda
W
Singsanan
Sanita
S
Fucharoen
Goonnapa
G
Fucharoen
Supan
S
D000328:Adult; D005192:Family Health; D005260:Female; D005838:Genotype; D006446:Hemoglobin E / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000235:genetics*; D017384:Sequence Deletion; D013785:Thailand; D017085:alpha-Thalassemia / Q000175:diagnosis / Q000235:genetics*; D055544:beta-Globins / Q000235:genetics*
D006455:Hemoglobins, Abnormal; D055544:beta-Globins; D006446:Hemoglobin E; C026447:hemoglobin Korle