{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T12:04:44Z","timestamp":1772107484783,"version":"3.50.1"},"reference-count":25,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematology Reports"],"abstract":"<jats:p>Background: Haemoglobinopathies are the most common monogenic disorders both in Greece and worldwide. The most effective strategies against them are carrier detection and prenatal testing following genetic risk assessment consultation for couples on the likelihood of their offspring being affected. Case Presentation: A novel alpha globin chain variant, named Hb Thessaloniki, was detected in Northern Greece. The underlying point variation HBA1:c.260T&gt;C (ref. seq. NM_000558.5) was detected in the HBA1 gene, in heterozygosity, during a routinely performed population screening for haemoglobinopathies. The amino-acid residue Leu86 was replaced by a structure disrupting Pro residue, resulting in a hyperunstable product as shown by the isopropanol test and predicted by the Dynamut2 and Alphafold3 algorithms. The haematological phenotype, due to which genetic analysis was performed, presented with mild microcytosis and hypochromia and was also indicative of the presence of an unstable haemoglobin produced in small quantities (variant encoded by HBA1). Since the proband\u2019s partner presented with a normal haematological phenotype, there is no risk of the couple giving birth to an affected offspring. Expanded analysis of the proband\u2019s relatives identified biallelic variants (\u03b1Parma\u03b1\/\u03b1\u03b1\u03a4hessaloniki) in the proband\u2019s mother, who presented with no apparent clinical findings, expect for slightly reduced haematological indices. Conclusions: The novel Hb Thessaloniki identified, although theoretically hyperunstable, seems to have minor effects on erythrocyte function, as indicated by haematological findings on the proband and his close relatives. Future identification of co-inheritance with HBA pathogenic point variations or deletions may provide further information regarding genetic counselling. In parallel, the usage of structure\u2013function relation-calculating algorithms may enhance our prediction capability for novel variants.<\/jats:p>","DOI":"10.3390\/hematolrep18020017","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T10:33:02Z","timestamp":1772101982000},"page":"17","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hb Thessaloniki, a Novel, Hyperunstable, Alpha Globin Variant Detected in Northern Greece"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0343-2434","authenticated-orcid":false,"given":"Effrossyni","family":"Boutou","sequence":"first","affiliation":[{"name":"Molecular Genetics Lab., Thalassaemia Unit, Center of Expertise in Rare Haematological Diseases (Haemoglobinopathies), Laikon General Hospital, 115 26 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3533-2182","authenticated-orcid":false,"given":"Nikos","family":"Papandreou","sequence":"additional","affiliation":[{"name":"Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, Panepistimiopolis, 157 71 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genovefa","family":"Mantzou","sequence":"additional","affiliation":[{"name":"Haemoglobinopathy Prevention Unit, Blood Bank Center, Hippokration Hospital of Thessaloniki, 546 42 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2043-9630","authenticated-orcid":false,"given":"Efthymia","family":"Vlachaki","sequence":"additional","affiliation":[{"name":"Thalassaemia Unit, Hippokration Hospital, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athanasios","family":"Vyzantiadis","sequence":"additional","affiliation":[{"name":"Haemoglobinopathy Prevention Unit, Blood Bank Center, Hippokration Hospital of Thessaloniki, 546 42 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christos","family":"Chassanidis","sequence":"additional","affiliation":[{"name":"Molecular Genetics Lab., Thalassaemia Unit, Center of Expertise in Rare Haematological Diseases (Haemoglobinopathies), Laikon General Hospital, 115 26 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Dimopoulou","sequence":"additional","affiliation":[{"name":"Thalassaemia Center, Center of Expertise in Rare Haematological Diseases (Haemoglobinopathies), Laikon General Hospital, 115 26 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angeliki","family":"Balassopoulou","sequence":"additional","affiliation":[{"name":"Molecular Genetics Lab., Thalassaemia Unit, Center of Expertise in Rare Haematological Diseases (Haemoglobinopathies), Laikon General Hospital, 115 26 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stamatia","family":"Theodoridou","sequence":"additional","affiliation":[{"name":"Haemoglobinopathy Prevention Unit, Blood Bank Center, Hippokration Hospital of Thessaloniki, 546 42 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kountouris, P., Lederer, C.W., Fanis, P., Feleki, X., Old, J., and Kleanthous, M. 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