title: Hb Cibeles [α2 CD25(B6) (Gly → Asp)]: a novel alpha chain variant causing alpha-thalassemia.
abstract: Thalassemias are the most frequent monogenic disorders around the world and are a serious health problem in areas with a high incidence. Thalassemias are particularly frequent in Mediterranean countries, the Middle East, Africa, the Indian subcontinent, and in the Southeast Asia. Of these, α-thalassemia is inherited as an autosomal recessive disorder. α-thalassemias are due to a deficiency or absence of hemoglobin (Hb) α-chain synthesis and are characterized by microcytic and hypochromic cells anemia and a clinical phenotype varying from nearly asymptomatic to a lethal hemolytic anemia. Compound heterozygotes and some homozygotes have a moderate to severe form of α-thalassemia called HbH disease. Hb Bart's hydrops fetalis is a lethal form in which no α-globin chain is synthesized. In this study we show a new structural variant of α-chain, Hb Cibeles [alpha 25(B6) Gly → Asp], in heterozygous state, which was undetectable by electrophoretic or chromatographic methods. Hb Cibeles is thus a hyper-unstable hemoglobinopathy. In this new globin chain variant, an apolar amino acid is replaced by a negatively charged amino acid. This change may be responsible for the molecular hyper-instability similar to the mutation in the adjacent residues.
authors.affiliation: Servicio de Hematología, Hospital Clínico San Carlos de Madrid, Profesor Martín Lagos s/n, 28040, Madrid, Spain, felixfuenteg@hotmail.com.
authors.forename: Félix
authors.initials: F
authors.lastname: de la Fuente-Gonzalo
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Nieto
authors.forename: Lara
authors.initials: L
authors.lastname: Vinuesa
authors.forename: Julián
authors.initials: J
authors.lastname: Sevilla
authors.forename: Joaquín
authors.initials: J
authors.lastname: Díaz-Mediavilla
authors.forename: Ana
authors.initials: A
authors.lastname: Villegas
authors.forename: Fernando A
authors.initials: FA
authors.lastname: González
authors.forename: Paloma
authors.initials: P
authors.lastname: Ropero
mesh_terms: D002675:Child, Preschool; D004252:DNA Mutational Analysis; D014644:Genetic Variation; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000175:diagnosis / Q000235:genetics*
chemical_list: D006455:Hemoglobins, Abnormal; D055542:alpha-Globins