title: Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia.
abstract: We describe here the molecular and hematological characteristics of novel frameshift mutations in exon 2 of the HBB gene (in heterozygous state) found in two Argentinean pediatric patients with dominant β-thalassemia-like features. In Hb Wilde, HBB:c.270_273delTGAG(p.Glu90Cysfs*67), we detected the deletion of the third base of the codon 89 (T) and the codon 90 (GAG), whereas in Hb Patagonia, HBB:c.296_297dupGT(p.Asp99Trpfs*59), the frameshift mutation was due to a duplication of a 'GT' dinucleotide after the second base of codon 98 (GTG). The Hb Patagonia and Hb Wilde mutations would result in elongated β-globin chains with modified C-terminal sequences and a total of 155 and 157 amino acids residues, respectively. Based on bioinformatics and structural analysis, as well as protein modeling, we predict that the elongated β-globins would affect the formation of the αβ dimers and their stability, which would further support the mechanism for the observed clinical features in both patients.
authors.affiliation: Cátedra de Genética y Biología Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Karen G
authors.initials: KG
authors.lastname: Scheps
authors.affiliation: Structural Bioinformatics Group, Unidad de Físico Química, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina.
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Hasenahuer
authors.affiliation: Structural Bioinformatics Group, Unidad de Físico Química, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Parisi
authors.affiliation: Structural Bioinformatics Group, Unidad de Físico Química, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina.
authors.forename: María S
authors.initials: MS
authors.lastname: Fornasari
authors.affiliation: Unidad de Hematología, Hospital de Niños 'Dr. Ricardo Gutiérrez', Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Sandra P
authors.initials: SP
authors.lastname: Pennesi
authors.affiliation: Servicio de Hematología, Unidad Asistencial 'Dr. César Milstein', Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Erramouspe
authors.affiliation: Unidad de Hematología, Hospital de Niños 'Dr. Ricardo Gutiérrez', Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Felisa N
authors.initials: FN
authors.lastname: Basack
authors.affiliation: Servicio de Hemato-Oncología Pediátrica, Hospital General de Niños 'Dr. Pedro de Elizalde', Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Ernesto S
authors.initials: ES
authors.lastname: Veber
authors.affiliation: Unidad de Hematología, Hospital de Niños 'Dr. Ricardo Gutiérrez', Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Luis
authors.initials: L
authors.lastname: Aversa
authors.affiliation: Servicio de Hemato-Oncología Pediátrica, Hospital General de Niños 'Dr. Pedro de Elizalde', Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Graciela
authors.initials: G
authors.lastname: Elena
authors.affiliation: Cátedra de Genética y Biología Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Viviana
authors.initials: V
authors.lastname: Varela
mesh_terms: D000293:Adolescent; D000328:Adult; D001772:Blood Cell Count; D002675:Child, Preschool; D003062:Codon; D004252:DNA Mutational Analysis; D004909:Erythrocyte Indices; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D014644:Genetic Variation; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation; D055503:Protein Multimerization; D055544:beta-Globins / Q000737:chemistry / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D003062:Codon; D006455:Hemoglobins, Abnormal; D055544:beta-Globins
keywords: HBB gene; dominant beta-thalassemia; elongated beta-globin variant; hemolytic anemia