title: Hb Youngstown [β101(G3)Glu → Ala; HBB: c.305A > C]: An unstable hemoglobin variant causing severe hemolytic anemia.
abstract: Hb Youngstown is a rare hemoglobin (Hb) variant caused by substitution of glutamic acid with alanine at amino acid residue 101 of the β-globin chain as a result of an A > C transversion on the β-globin gene nucleotide sequences [β101(G3)Glu → Ala; HBB: c.305A > C]. We now report three patients from two different families, one from South Africa and the other from Costa Rica, who are heterozygous for this Hb variant. All three carriers had marked hemolysis, consistent with Hb Youngstown being a highly unstable variant. The substitution of glutamic acid, a large and negatively charged amino acid, with alanine, a small and non polar amino acid, in the interface of the α1- and β2-globin subunits might interfere with the transition between the oxy- and deoxyHb, and lead to Hb instability and hemolytic anemia.
authors.affiliation: Departments of Medicine, and Pathology and Laboratory Medicine, Division of Hematology/Oncology, Boston University School of Medicine , Boston, Massachusetts , USA .
authors.forename: Heather L
authors.initials: HL
authors.lastname: Edward
authors.forename: Louis Almero Du
authors.initials: LA
authors.lastname: Pisani
authors.forename: Walter E
authors.initials: WE
authors.lastname: Rodriguez-Romero
authors.forename: Jorge
authors.initials: J
authors.lastname: Chaves-Villalobos
authors.forename: Jonielle
authors.initials: J
authors.lastname: Garcia-Quesada
authors.forename: Neil S
authors.initials: NS
authors.lastname: Harris
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Luo
authors.forename: Martin H
authors.initials: MH
authors.lastname: Steinberg
authors.forename: Bernard G
authors.initials: BG
authors.lastname: Forget
authors.forename: David H K
authors.initials: DH
authors.lastname: Chui
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D000745:Anemia, Hemolytic, Congenital / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002648:Child; D005260:Female; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense; D055550:Protein Stability
chemical_list: D006455:Hemoglobins, Abnormal; C000613952:hemoglobin Youngstown
keywords: De novo mutation; Hb Youngstown; hemolytic anemia; unstable hemoglobin (Hb)