title: Beta thalassemia IVS-I-5(G-->C) heterozygosity masked by the presence of HbJ-Meerut in a Dutch-Indian patient.
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.
authors.affiliation: Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. p.c.giordano@lumc.nl
authors.forename: Piero C
authors.initials: PC
authors.lastname: Giordano
authors.forename: R G H J
authors.initials: RG
authors.lastname: Maatman
authors.forename: R W L M
authors.initials: RW
authors.lastname: Niessen
authors.forename: Peter
authors.initials: P
authors.lastname: van Delft
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Harteveld
mesh_terms: D000328:Adult; D001797:Blood Protein Electrophoresis; D002851:Chromatography, High Pressure Liquid; D005188:False Negative Reactions; D005260:Female; D005914:Globins / Q000235:genetics*; D006443:Hemoglobin A2 / Q000032:analysis* / Q000737:chemistry / Q000302:isolation & purification; D006448:Hemoglobin J / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D006452:Hemoglobinometry / Q000379:methods*; D006579:Heterozygote; D006801:Humans; D007194:India / Q000208:ethnology; D009426:Netherlands; D010641:Phenotype; D017086:beta-Thalassemia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics
chemical_list: C060130:hemoglobin J Meerut; D006448:Hemoglobin J; D005914:Globins; D006443:Hemoglobin A2