Heterocellular hereditary persistence of fetal haemoglobin affects the haematological parameters of beta-thalassaemia trait.
To assess and define the effects of heterocellular hereditary persistence of fetal haemoglobin (HPFH) on the haematological phenotype of heterozygous beta-thalassaemia, we have studied a large kindred that included a total of 204 subjects with 60 beta-thalassaemia carriers, of whom 35 were also heterozygous, and five homozygous, for heterocellular HPFH. The study was possible because of the homogeneity of the beta-thalassaemia mutation and the ability to genotype the heterocellular HPFH allele. Heterocellular HPFH had a significant effect on the mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV) and haemoglobin (Hb) A2 values in the beta-thalassaemia carriers and accounted for 29%, 30% and 24% of their respective variances. beta-thalassaemia subjects with heterocellular HPFH had higher MCV and MCH values, concomitant with lower levels of Hb A2, and a reduced ineffective erythropoiesis. We conclude that co-inheritance of heterocellular HPFH leads to a primary increase in gamma-chain synthesis in beta-thalassaemia trait and can be another confounding factor in the use of red cell indices and Hb A2 levels in population screening for beta-thalassaemia.
Garner
Chad
C
Department of Environmental Analysis and Design, Division of Epidemiology, University of California, Irvine, CA, USA.
Dew
Tracy K
TK
Sherwood
Roy
R
Rees
David
D
Thein
Swee Lay
SL
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002648:Child; D004909:Erythrocyte Indices; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis*; D005838:Genotype; D006443:Hemoglobin A2 / Q000032:analysis; D006453:Hemoglobinopathies / Q000150:complications* / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008403:Mass Screening; D010641:Phenotype; D017086:beta-Thalassemia / Q000150:complications* / Q000175:diagnosis / Q000235:genetics
D006443:Hemoglobin A2; D005319:Fetal Hemoglobin