Written by Ms Maria Xeniphontos, Cyprus Institute of Neurology and Genetics, Cyprus
Structural haemoglobinopathies are genetic disorders characterized by abnormalities in the structure of haemoglobin (Hb), the oxygen-carrying protein found in red blood cells. These abnormalities result from pathogenic variants affecting the amino acid sequence of the globin chains causing alterations in the functional domains of the haemoglobin molecule or its overall structure.
These conditions encompass a wide range of variants, including those that lead to an unstable haemoglobin tetramer or alter haemoglobin’s affinity for oxygen. Additionally, variants can cause erythrocyte deformation or haemolysis under certain conditions, such as sickling variants.
The terminology used to annotate structural haemoglobin variants often lacks clarity, as it combines the variant’s impact on protein properties with the mode of disease inheritance (e.g., Thalassemia dominant variants). Moreover, sometimes the same term is used to denote variants with varying effects. For instance, the term “unstable Hbs” may encompass variants that range from having no clinical significance to causing mild to severe haemolytic anaemia.
To address this issue, Ms Maria Xenophontos, a bioinformatics researcher at the Cyprus Institute of Neurology and Genetics, collaborated with Prof. Celeste Bento, an expert laboratory geneticist at Coimbra University Hospital (CHUC), in Portugal, for a short-term scientific mission (STSM) funded by the HELIOS COST Action CA22119. During the STSM, the researchers worked on developing a glossary aimed at providing distinct definitions for terms used in the field with regard to the mode of inheritance per disease and its effect on haemoglobin structure, to facilitate the harmonisation of annotation practices. Additionally, case-level data were retrieved from the ITHANET portal (https://ithanet.eu) and were employed to refine the quality of variant annotations on the portal. The results of the STSM will accompany a literature review on structural hemoglobinopathies.
Reflecting on the experience, Prof. Celeste Bento underscored the significance of collaborative work across diverse areas of expertise such as molecular genetics and bioinformatics. She highlighted how this collaborative effort enabled a thorough exploration of the nomenclature for haemoglobinopathies, describing it as “an intense experience that fostered the exchange of expertise among all participants”.
In alignment with the sentiment, Ms Maria Xenophontos expressed her endorsement of the STSM program to all members of the HELIOS action. She emphasized not only the productivity achieved through collaborative work but also the value of scientific discussions and shared experiences outside the lab, which contributed to the advancement of collaborations.
Funded by HELIOS COST Action CA22119