Журнал генетических синдромов и генной терапии
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Hb Nunobiki [α₂ 141(HC3) Arg→Cys; HBA2:c.424C>T] in Spain: Mutation de novo or Acquired?

Ropero P, González-Borrachero ML, Peña A, González FA, Fuente-Gonzalo F de la, Martínez J, Vinuesa L, Villegas A and Díaz-Mediavilla J

The most common hemoglobin arose as an adaptation to the environment and its expansion was carried out by mechanisms of gene flow and population growth related to the social changes of habits of mankind. Other hemoglobinopathies (Hbs) to have low prevalence and appear in population studies of Hb or glycosylated hemoglobin (Hb A1c). Most of these Hbs have been identified in isolation and individually, others in a few families, considering these cases de novo mutations or that the mutated gene has been transported inadvertently. An example is Hb Nunobiki, discovered in Japan and Belgium. We report 7 cases from four families in Andalusia, identified during the quantification of Hb A1c. In all cases, both by capillary electrophoresis and ion exchange HPLC (II-HPLC), HBX appeared faster than HbA. By reverse phase HPLC eluted globin chain slower than αA, αX. Sequencing of gene α2 shown the substitution (CGT>TGT) in exon 3 CD141(Arg>Cys)→Hb Nunobiki. This hemoglobin has increased affinity for oxygen but was not detected by polycythemia due to the low percentage of variant since it is α chain, but because it showed during the determination of Hb A1c. This fact confirms that the II-HPLC is the gold standard for identification of hemoglobinopathies. The quantification of Hb A1c, by HPLC can identify structural Hb variants that otherwise would not have been detected and are clinically silent but may help clarify the evolution, adaptation and distribution of hemoglobin to the medium.