title: A Clinical Update of the Hb Siirt [β27(B9)Ala→Gly; HBB: c.83C>G] Hemoglobin Variant.
abstract: We report a clinical update of the hemoglobin (Hb) variant [β27(B9)Ala→Gly; HBB: c.83C>G], named Hb Siirt, that was previously described as a silent variant in a 23-year-old Kurdish female. The patient was also a carrier of the codon 5 (-CT) (HBB: c.17_18delCT) frameshift mutation and of the αααanti 3.7triplication. Her initial moderate β-thalassemia intermedia (β-TI) phenotype worsened with time, causing the patient to become a transfusion-dependent subject at the age of ∼40 years. Subsequent molecular characterization of both parents revealed that the Hb Siirt variant was inherited by the mother, while the other two globin alterations (HBB: c.17_18delCT and αααanti 3.7triplication) were genetically transmitted by the father. The latter remained a carrier of a mild β-TI phenotype throughout his life, at least until the age of 65 years. We hypothesize that the worsened clinical conditions in the daughter were due to the additional, maternally inherited Hb Siirt variant. However, protein 3D conformational analysis did not seem to reveal substantial overall structural changes. Among the other three described variants [Hb Volga (HBB: c.83C>A), Hb Knossos (HBB: c.82 G>T), Hb Grange-Blanche (HBB: c.83C>T] that are due to nucleotide substitutions at codon 27 of the β-globin gene; only Hb Knossos causes a β+-thalassemia (β+-thal) phenotype.
authors.affiliation: a Azzociazione Nazionale per la lotta alla Microcitemia in Italia (ANMI) Onlus, Centro Studi Microcitemie Roma , Roma , Italia.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Cappabianca
authors.affiliation: b Facoltà di Bioscienze e Tecnologie Agro-Alimentari e Ambientali, Università di Teramo , Teramo , Italia.
authors.forename: Alessia
authors.initials: A
authors.lastname: Colosimo
authors.affiliation: b Facoltà di Bioscienze e Tecnologie Agro-Alimentari e Ambientali, Università di Teramo , Teramo , Italia.
authors.forename: Annalaura
authors.initials: A
authors.lastname: Sabatucci
authors.affiliation: b Facoltà di Bioscienze e Tecnologie Agro-Alimentari e Ambientali, Università di Teramo , Teramo , Italia.
authors.forename: Enrico
authors.initials: E
authors.lastname: Dainese
authors.affiliation: a Azzociazione Nazionale per la lotta alla Microcitemia in Italia (ANMI) Onlus, Centro Studi Microcitemie Roma , Roma , Italia.
authors.forename: Paola
authors.initials: P
authors.lastname: Di Biagio
authors.affiliation: a Azzociazione Nazionale per la lotta alla Microcitemia in Italia (ANMI) Onlus, Centro Studi Microcitemie Roma , Roma , Italia.
authors.forename: Roberta
authors.initials: R
authors.lastname: Piscitelli
authors.affiliation: a Azzociazione Nazionale per la lotta alla Microcitemia in Italia (ANMI) Onlus, Centro Studi Microcitemie Roma , Roma , Italia.
authors.forename: Ofelia
authors.initials: O
authors.lastname: Sarra
authors.affiliation: a Azzociazione Nazionale per la lotta alla Microcitemia in Italia (ANMI) Onlus, Centro Studi Microcitemie Roma , Roma , Italia.
authors.forename: Daniela
authors.initials: D
authors.lastname: Zei
authors.affiliation: a Azzociazione Nazionale per la lotta alla Microcitemia in Italia (ANMI) Onlus, Centro Studi Microcitemie Roma , Roma , Italia.
authors.forename: Antonio
authors.initials: A
authors.lastname: Amato
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D003062:Codon; D004909:Erythrocyte Indices; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D010100:Oxygen / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D055815:Young Adult; D055542:alpha-Globins / Q000235:genetics; D055544:beta-Globins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017086:beta-Thalassemia / Q000097:blood / Q000175:diagnosis / Q000235:genetics
chemical_list: D003062:Codon; D006455:Hemoglobins, Abnormal; D055542:alpha-Globins; D055544:beta-Globins; D006418:Heme; D010100:Oxygen
keywords: Kurdish; codon 27; hemoglobin (Hb) variant; β-Thalassemia intermedia (β-TI)