title: New and known β-thalassemia determinants masked by known and new δ gene defects [Hb A(2)-Ramallah or δ6(A3)Glu→Gln, GAG>>CAG].
abstract: We report a novel thalassemia determinant found in a Nigerian woman living in the Netherlands, resulting from a 2 bp insertion at codons 9/10 of the β-globin gene (HBBc.28_29insTA p.Ser10LeufsX11). The novel defect causes a frameshift with a consequent premature TGA stop codon, located at 11 positions downstream from the mutated codon. The phenotype was typical of a β-thalassemia (β-thal), trait with high RBC counts and compensated mild microcytic anemia. However, the Hb A(2) level was reported to be normal due to the presence of the common Hb A(2)' or Hb B2 [δ16(A13)Gly→Arg, GGC>CGC] variant that was not taken into account. We also present the opposite but comparable situation found in an a Palestinian man living in the USA. He was a carrier of a common β-globin gene defect [codon 6 (-A), HBB:c.20delA] in combination with a novel δ-globin gene defect at codon 6 [HBD. c.19G>C, Glu6Gln] that we have named Hb A(2)-Ramallah. In both cases, the provisional diagnosis could have been compromised when based on the measurement of the normal Hb A(2) fraction only.
authors.affiliation: The Reference Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marion
authors.initials: M
authors.lastname: Phylipsen
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Harteveld
authors.forename: Menno
authors.initials: M
authors.lastname: de Metz
authors.forename: Monica V E
authors.initials: MV
authors.lastname: Gallivan
authors.forename: Sandra G J
authors.initials: SG
authors.lastname: Arkesteijn
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Luo
authors.forename: David H K
authors.initials: DH
authors.lastname: Chui
authors.forename: Piero C
authors.initials: PC
authors.lastname: Giordano
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005260:Female; D006455:Hemoglobins, Abnormal / Q000032:analysis / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics*; D055546:delta-Globins / Q000235:genetics*
chemical_list: D006455:Hemoglobins, Abnormal; D055544:beta-Globins; D055546:delta-Globins; C556239:hemoglobin A(2)-Ramallah