title: Hb Iberia [α104(G11)Cys → Arg,TGC>CGC (α2) (HBA2:c.313T>C)], a new α-thalassemic hemoglobin variant found in the Iberian Peninsula: report of six cases.
abstract: We report a new structural defect of the α2-globin chain presenting with moderate microcytic hypochromic anemia, in six individuals from three unrelated families, living in Portugal and Spain. α-Globin gene deletions were ruled out by gap-polymerase chain reaction (gap-PCR) and multiplex ligation-dependent probe amplification (MLPA). Direct sequencing of the α2-globin gene revealed a substitution of codon 104 [α104(G11)Cys→Arg, TGC>CGC (α2) (HBA2:c.313T>C)]. This new variant, not detectable by high performance liquid chromatography (HPLC) or electrophoresis, was called Hb Iberia, as it was observed for the first time in families from the Iberian Peninsula.   Although the mutant allele is transcribed, as indicated by the balanced mRNA α/β ratio, the abnormal α2 chain could not form a stable tetramer as the cysteine and arginine residues, located at the α1β1 contact, differ in size, charge and hydrophobicity.   Hb Iberia is the third mutation described at codon 104 on the α-globin genes, namely, Hb Sallanches (α2, TGC>TAC) and Hb Oegstgeest (α1, TGC>AGC), also characterized as unstable hemoglobins (Hbs), present on an α-thalassemic phenotype.
authors.affiliation: Centro Hospitalar e Universitário de Coimbra, Serviço de Hematologia, Coimbra, Portugal. celeste.bento@chc.min-saude.pt
authors.forename: Celeste
authors.initials: C
authors.lastname: Bento
authors.forename: Ana Catarina
authors.initials: AC
authors.lastname: Oliveira
authors.forename: Joana
authors.initials: J
authors.lastname: Neves
authors.forename: Mariline
authors.initials: M
authors.lastname: Gameiro
authors.forename: Elizabete
authors.initials: E
authors.lastname: Cunha
authors.forename: Margarida
authors.initials: M
authors.lastname: Coucelo
authors.forename: Ricardo Marques
authors.initials: RM
authors.lastname: Costa
authors.forename: José
authors.initials: J
authors.lastname: Barbot
authors.forename: Emilia
authors.initials: E
authors.lastname: Costa
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Lago
authors.forename: M Leticia
authors.initials: ML
authors.lastname: Ribeiro
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D001483:Base Sequence; D003062:Codon; D005091:Exons; D005260:Female; D005838:Genotype; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D017354:Point Mutation; D011174:Portugal; D011487:Protein Conformation; D013030:Spain; D055815:Young Adult; D055542:alpha-Globins / Q000737:chemistry / Q000235:genetics*; D017085:alpha-Thalassemia / Q000175:diagnosis / Q000235:genetics*
chemical_list: D003062:Codon; D006455:Hemoglobins, Abnormal; D055542:alpha-Globins; C580754:hemoglobin Iberia