Beta thalassemia IVS-I-5(G-->C) heterozygosity masked by the presence of HbJ-Meerut in a Dutch-Indian patient

Haematologica. 2006 Dec;91(12 Suppl):ECR56.

Abstract

We describe the genotype/phenotype correlation in a 35 year old anemic female referred to our laboratory because a fast eluting minor fraction on HPLC, mild hemolysis and hematological parameters suggesting a Thalassemia trait, eventually in combination with iron depletion. Direct sequencing of the alpha globin genes revealed heterozygosity for HbJ-Meerut, a Glu-->Ala substitution at residue 120 not justifying the hematological parameters. No other point mutations were found on the alpha genes and Gap-PCR excluded the 6 common deletion defects. Direct sequencing of the beta-globin genes revealed the IVS-I-5 (G-->C) transversion in absence of the elevated HbA2 levels usually measured in carriers of this beta-Thalassemia mutation. The HbA2 tetramer in the presence of HbJ-Meerut divides in two parts. One alphaN2/delta2 migrating on the right spot on HPLC. The other alphaJ2/delta2 migrating under the HbA fraction. Classic alkaline electrophoresis and the modern capillary electrophoresis CE showed these two tetramers and the reduction of the elevated HbA2 level of the beta-Thalassemia trait by at least 20% due to HbA2 Meerut.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Blood Protein Electrophoresis
  • Chromatography, High Pressure Liquid
  • False Negative Reactions
  • Female
  • Globins / genetics*
  • Hemoglobin A2 / analysis*
  • Hemoglobin A2 / chemistry
  • Hemoglobin A2 / isolation & purification
  • Hemoglobin J / analysis*
  • Hemoglobin J / chemistry
  • Hemoglobin J / genetics
  • Hemoglobinometry / methods*
  • Heterozygote
  • Humans
  • India / ethnology
  • Netherlands
  • Phenotype
  • beta-Thalassemia / blood
  • beta-Thalassemia / diagnosis*
  • beta-Thalassemia / genetics

Substances

  • hemoglobin J Meerut
  • Hemoglobin J
  • Globins
  • Hemoglobin A2