Interaction of hemoglobin E and several forms of alpha-thalassemia in Cambodian families.
OBJECTIVE
This study aimed to describe hematologic and molecular characterization of the interaction of hemoglobin (Hb) E and several forms of alpha-thalassemia causing complex thalassemia syndromes in two Cambodian families as well as to establish a rapid polymerase chain reaction (PCR) assay for simultaneous detection of Hb Constant Spring (CS) and Hb Pakse' (PS).


METHODS
Using PCR and DNA sequencing, the alpha- and beta-globin genotypes were examined. Clinical and hematologic data were assessed. A multiplex asymmetric allele-specific PCR for differential diagnosis of HbCS and HbPS was developed and validated.


RESULTS
Eight genotypes including heterozygous HbCS, heterozygous HbPS, double heterozygous HbE/HbPS, double heterozygous HbE/alpha-thalassemia 2, triple heterozygous HbE/alpha-thalassemia /HbPS, homozygous HbE/alpha-thalassemia 2, compound alpha-thalassemia 2/HbCS and a hitherto undescribed compound HbCS/HbPS were found in these two families. Genotype-phenotype relationships are discussed and successful application of a multiplex PCR system for differential diagnosis of HbCS and HbPS is described.


CONCLUSIONS
The interaction of several globin gene abnormalities in Cambodian families emphasizes the high frequencies of thalassemia and hemoglobinopathies. Identification of HbPS suggests that this mutation might be common and underestimated among South-east Asian populations. A simplified PCR assay for simultaneous detection of HbCS and HbPS would facilitate characterization of these genotypes in both the clinical setting and population screening programs in the region.
Fucharoen
Supan
S
Department of Clinical Chemistry, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand, 40002. supan@kku.ac.th
Sanchaisuriya
Kanokwan
K
Fucharoen
Goonnapa
G
Panyasai
Sitthichai
S
Devenish
Robyn
R
Luy
Lyda
L
D000293:Adolescent; D000328:Adult; D000483:Alleles; D002160:Cambodia; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006446:Hemoglobin E / Q000235:genetics / Q000378:metabolism*; D006455:Hemoglobins, Abnormal / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D025941:Protein Interaction Mapping / Q000379:methods*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017085:alpha-Thalassemia / Q000235:genetics / Q000378:metabolism*
D006455:Hemoglobins, Abnormal; D020033:Protein Isoforms; C099132:hemoglobin Pakse; D006446:Hemoglobin E; C035541:Hemoglobin Constant Spring