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We present here five new hemoglobin (Hb) variants which have been identified during routine Hb analysis before their genotypic characterization. Four of these result from a classical missense mutation: Hb Canuts [α85(F6)Asp→His (α1)], Hb Ambroise Pare [α117(GH5)Phe→Ile (α2)], Hb Beaujolais [β84(EF8)Thr→Asn] and HbA2-North Africa [δ59(E3)Lys→Met]. The last one, Hb Monplaisir [β147 (Tyr-Lys-Leu-Ala-Phe-Phe-Leu-Leu-Ser-Asn-Phe-Tyr-158-COOH)], results from a frameshift mutation at the stop codon of the β-globin gene which leads to a modified C-terminal sequence in the β-globin chain. None of these variants seem to have a particular clinical expression in the heterozygous state. The circumstances of the discovery of these five new Hb variants emphasize the fact that an association of techniques is necessary for a complete screening of Hb variants during routine Hb analysis. Globin chain separation by reversed phase liquid chromatography (RP‐LC) appears to be the most relevant method.

A new hemoglobin (Hb) variant in the heterozygous state, Hb Al-Hammadi Riyadh [codon 75 (GAC→GTC); α75(EF4)Asp→Val (α2)] corresponding to an A→T transversion on the second exon of the α2-globin gene, is described. The variant was characterized by DNA sequencing and mass spectrometry (MS). The variant was found during a routine Hb analysis for anemia in a 16-month-old boy who lived in Riyadh, Kingdom of Saudi Arabia.

A new G(gamma) hemoglobin (Hb) variant, Hb F-Bron [gamma20(B2)Val-->Ala] on the first exon of the G(gamma)-globin gene is described. The variant was characterized by DNA sequencing and mass spectrometry (MS). Hematological abnormalities included hypochromia and microcytosis and were probably caused by an interaction with an alpha-thalassemia (thal) (3.7 kb) deletion in the heterozygous state.

Two new hemoglobin (Hb) variants: Hb Brem-sur-Mer [codon 9 (TC T→TA T); β9(A6)Ser→Tyr] on the first exon of the β-globin gene and Hb Passy [codon 81 (T CC→C CC); α81(F2)Ser→Pro (α2)] on the second exon of the α2-globin gene, are described. The two variants were characterized by DNA sequencing and mass spectrometry (MS). Hematological abnormalities: microcytosis and hypochromia were found only in the carrier of Hb Passy. In the absence of an association with an α-thalassemic deletion or mutation, the mutation 81(F2)Pro could induce a possible α-thalassemia (thal).

Hemoglobin Lyon-Bron was found in two members of a family of German ascent presenting with a moderate normocytic anemia. In this alpha2 globin variant, the N-terminal valine of the chain was replaced by an alanine. Electrospray mass spectrometry of the α chain showed that, as normally, the initiator methionine was cleaved during globin processing but that the Nα-terminal group was totally acetylated. This resulted in structural modifications of a region crucial for oxygen binding. As a consequence, hemoglobin Lyon-Bron displayed both a reduced chloride effect and a decreased oxygen affinity, this last point explaining the apparent anemia. Am. J. Hematol. 69:214–218, 2002. © 2002 Wiley-Liss, Inc.

During routine hemoglobin (Hb) investigations for a possible hemoglobinopathy, performed on a 6-year-old boy suffering from mild microcytic anemia, an abnormal Hb was detected by cation exchange hi...

Hemoglobin Debrousse (beta 96[FG3]Leu-->Pro) is a new unstable variant, with high oxygen affinity responsible, in the steady state, for an apparently well-compensated chronic hemolytic anemia. The functional properties of this variant are due to the replacement of a leucine residue which is involved in the hydrophobic environment of the proximal side of the heme. This electrophoretically neutral hemoglobin was found as a de novo case in a 6-year-old girl suffering from severe anemia with hemolysis and transient aplastic crisis, following infection by parvovirus B19.

DNA analysis is currently the easiest way to identify a hemoglobin variant in most cases. Nevertheless, in case of complex gene rearrangements, mass spectrometry studies may be required to orientate the DNA diagnosis. The present report shows the use of mass spectrometry techniques prior to DNA analysis for the identification of the rare P-Nilotic fusion hemoglobin. Complete protein analysis is performed by liquid chromatography–tandem mass spectrometry on the abnormal globin chain isolated by reversed-phase liquid chromatography.

During routine studies of a patient who presented with venous thrombosis and erythrocytosis, a high affinity hemoglobin (Hb) variant, Hb Milledgeville [α44(CE2)Pro→Leu (α2)], was found. The patient...