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Updated: Oct 2, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
New alpha 2 globin chain variant with low oxygen affinity affecting the N-terminal residue and leading to
1Unité de Pathologie Moléculaire, Département de Biochimie, Hôpital Edouard Herriot, Lyon, France.
Abstract:
Hemoglobin Lyon-Bron was found in two members of a family of German ascent presenting with a moderate normocytic anemia. In this alpha 2 globin variant, the N-terminal valine of the chain was replaced by an alanine. Electrospray mass spectrometry of the alpha chain showed that, as normally, the initiator methionine was cleaved during globin processing but that the N alpha-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.
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