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We report a novel mutation on the β-globin gene in a 68-year-old woman of Sicilian origin living in Alessandria, Italy. This mutation produces a hemoglobin (Hb) variant of Hb A that was detected by the capillary electrophoresis (CE) method during measurement of Hb A

Objectives The observation of numerous new structural defects in hemoglobin (Hb) has often been linked to the evolution and development of device technologies used for the separation and quantification of hemoglobin components. However, the increased use of preventive tests for hemoglobinopathies and separative methods to quantify glycated hemoglobin (HbA1c) also contributed to these observations, as demonstrated by the case described here. Our aim is to emphasize that different separative method can provide more useful information in patient management. Methods A 64-year-old diabetic woman of Moroccan descent was examined in the context of HbA1c monitoring. The test was performed using high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) systems. Molecular characterization was performed by direct sequencing of the β and α globin genes. Results The two methods used showed the presence of an anomalous fraction identified as HbS, already observed previously, but only through CE it was possible to observe the presence of another variant and its hybrid components. Direct sequencing of β and α globin genes confirmed heterozygous HbS [β6 (A3) Glu→Val; HBB: c.20A>T] and allowed to identify a mutation on the α 2, [α114 (GH2) Pro→Leu gene; HBA2: c.344C>T] corresponding to the rare Hb Nouakchott variant. Conclusions The two Hb variants highlighted by the EC and the molecular characterization therefore allowed adequate advice, the correct assessment of HbA1c and metabolic status and therefore better clinical management of the patient. The availability of different instruments in the same laboratory, confirming situations of diagnostic uncertainty, represents a valuable opportunity that should be encouraged.

Artifactually altered glycated hemoglobin (HbACation exchange high performance liquid chromatography (HPLC) (Bio-Rad Variant™ II; Trinity Biotech Premier Hb9210 Resolution), capillary electrophoresis (CE) (Sebia Capillarys 2 Flex Piercing) and mass spectrometry (MS) (Waters) were used for variant detection; Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA) and next generation sequencing (NGS) were used for DNA analysis; HbAHb Yamagata [β132(H10)Lys→Asn; (A mosaicism of Hb Yamagata was found in a patient with altered HbA