title: Distinct phenotypic expression associated with a new hyperunstable alpha globin variant (Hb heraklion, alpha1cd37(C2)Pro>0): comparison to other alpha-thalassemic hemoglobinopathies.
abstract: Clinical phenotypes associated with abnormal globin chain biosynthesis may result in thalassemia (deficient quantity) or hemolytic anemia (abnormal hemoglobins). However, the phenotypic expression of hyperunstable hemoglobin variants often includes features of thalassemia, along with variable peripheral hemolysis. Hemoglobinopathies caused by highly unstable beta-chain variants have a dominant thalassemia-like phenotype, in which carriers have a clinical expression of thalassemia intermedia, but highly unstable alpha-globin variants are usually only phenotypically apparent when they interact with other alpha-thalassemia mutations. In a child with clinical and hematological features consistent with beta-thalassemia intermedia, DNA analysis excluded any beta-globin gene mutations but characterized a novel deletion cd37(C2)Pro>0 (Hb Heraklion) in the alpha1 globin gene, in trans to a common Mediterranean nondeletion alpha-thalassemia mutation (alpha(Hph)alpha). The deletion of proline at alpha37(C2) is predicted to result in severe instability of the variant hemoglobin, which on interaction with a synthesis-deficient alpha-thalassemia mutation causes a relatively severe dyserythropoietic anemia, representing an alternative phenotype associated with highly unstable alpha-chain variants. Hb Heraklion is the fourth highly unstable alpha-globin variant that we have observed in patients from Greece and Albania. Two variants involve the alpha2-globin gene: Hb Agrinio (alpha29(B10)Leu>Pro) and Hb Adana (alpha59(E8)Gly>Asp), and two the alpha1-gene: Hb Aghia Sophia (alpha62(E11)Val>0) and (Hb Heraklion a37(C2)Pro>0). Each has been observed on interaction with a different alpha-thalassemia mutation and the phenotypes associated with these highly unstable alpha-variants are presented.
authors.affiliation: First Department of Pediatrics, University of Athens, St. Sophia's Children's Hospital, Athens, 11527, Greece.
authors.forename: J
authors.initials: J
authors.lastname: Traeger-Synodinos
authors.forename: I
authors.initials: I
authors.lastname: Papassotiriou
authors.forename: A
authors.initials: A
authors.lastname: Metaxotou-Mavrommati
authors.forename: C
authors.initials: C
authors.lastname: Vrettou
authors.forename: A
authors.initials: A
authors.lastname: Stamoulakatou
authors.forename: E
authors.initials: E
authors.lastname: Kanavakis
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005914:Globins / Q000737:chemistry / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D010641:Phenotype; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D017086:beta-Thalassemia / Q000235:genetics* / Q000473:pathology
chemical_list: D006455:Hemoglobins, Abnormal; D005914:Globins; D004247:DNA