title: A Mosaic Expression of a Hb J-Amiens (HBB: c.54G > T; p.Lys18Asn) and its Interference with Hb A1c Analysis.
abstract: We report the case of a 56-year-old Caucasian woman in whom hemoglobinopathy screening was triggered following an aberrant Hb A1c analysis. Preliminary diagnosis of the hemoglobin (Hb) variant was obtained through cation exchange high performance liquid chromatography (HPLC) and gel electrophoresis. DNA analysis confirmed the presence of Hb J-Amiens [β17(A14)Lys→Asn; HBB: c.[54G > C or 54G > T)]. However, an unbalanced ratio between wild type and mutant signal after direct sequencing and a lower than expected percentage of this Hb variant led to the suggestion of a mosaic expression. Furthermore, different methods [capillary zone electrophoresis (CZE), cation exchange HPLC and boronate affinity] were tested to study the possible interference of this variant with Hb A1c measurements. These investigations showed a clinically relevant difference between the methods tested. Hb A1c analysis may lead to the discovery of new Hb variants or mosaicism for previously described Hb variants. This may have genetic consequences for the offspring of carriers and brings about the question of partner testing.
authors.affiliation: a Department of Laboratory Medicine , University Hospitals Leuven , Leuven , Belgium.
authors.forename: Toon
authors.initials: T
authors.lastname: Schiemsky
authors.affiliation: b Department of Laboratory Medicine , Onze-Lieve-Vrouwziekenhuis Hospital Aalst , Aalst , Belgium.
authors.forename: Lieve
authors.initials: L
authors.lastname: Van Hoovels
authors.affiliation: a Department of Laboratory Medicine , University Hospitals Leuven , Leuven , Belgium.|c Department of Cardiovascular Sciences , Katholieke Universeit Leuven, University of Leuven , Leuven , Belgium.
authors.forename: Koen J O
authors.initials: KJ
authors.lastname: Desmet
authors.affiliation: d Klinische Genetica Laboratory for Diagnostic Genome Analysis, Haemoglobinopathies Laboratory, Leiden University Medical Center , Leiden , The Netherlands.
authors.forename: Marion
authors.initials: M
authors.lastname: Phylipsen
authors.affiliation: d Klinische Genetica Laboratory for Diagnostic Genome Analysis, Haemoglobinopathies Laboratory, Leiden University Medical Center , Leiden , The Netherlands.
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Harteveld
authors.affiliation: a Department of Laboratory Medicine , University Hospitals Leuven , Leuven , Belgium.|c Department of Cardiovascular Sciences , Katholieke Universeit Leuven, University of Leuven , Leuven , Belgium.
authors.forename: Davy M J
authors.initials: DM
authors.lastname: Kieffer
mesh_terms: D019943:Amino Acid Substitution; D003062:Codon; D004252:DNA Mutational Analysis; D004909:Erythrocyte Indices; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006442:Glycated Hemoglobin / Q000235:genetics* / Q000378:metabolism; D006448:Hemoglobin J / Q000235:genetics* / Q000378:metabolism*; D006453:Hemoglobinopathies / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D055544:beta-Globins / Q000235:genetics
chemical_list: D003062:Codon; D006442:Glycated Hemoglobin; D006448:Hemoglobin J; D055544:beta-Globins; C067280:hemoglobin J-Amiens
keywords: Hb A1c interference; Hb J-Amiens; Hemoglobin (Hb) variant; mosaic