title: A Novel β-Globin Chain Hemoglobin Variant, Hb Allentown [β137(H15)Val→Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp], Associated with Low Oxygen Saturation, Intermittent Aplastic Crises and Splenomegaly.
abstract: Hemoglobin (Hb) variants may be associated with low oxygen saturation and exacerbated episodes of anemia from common stressors such as viral infections. These attributes frequently cause increased clinical concern and unnecessary and expensive testing if not considered early in the evaluation of the patient. Some clinically significant Hb variants result in a normal Hb electrophoresis result, which can be method-dependent. Herein we describe a patient with low oxygen saturation and a history of hemolytic anemia who was subsequently found to carry a novel, unstable β-globin variant that we have named Hb Allentown [β137(H15)Val→Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp] for the place of identification of the variant. Hb Allentown is formed by a rare double nucleotide substitution within the same codon. Additionally, positive identification of rare Hb variants characterized by a single method is discouraged, as the Hb variant was misclassified as Hb S-South End or β6(A3)Glu→Val;β132(H10)Lys→Asn (HBB: c.[20A > T;399A > C]) by the initial laboratory.
authors.affiliation: a Department of Pediatrics , Division of Pediatric Hematology-Oncology, University of Mississippi Medical Center , Jackson, Mississippi , USA.
authors.forename: Anderson B
authors.initials: AB
authors.lastname: Collier
authors.affiliation: b Departments of Laboratory Medicine and Pathology , Hematopathology, Mayo Clinic , Rochester, Minnesota , USA.
authors.forename: Lea M
authors.initials: LM
authors.lastname: Coon
authors.affiliation: c Department of Pediatrics , Lehigh Valley Health Network , Allentown, Pennsylvania , USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Monteleone
authors.affiliation: c Department of Pediatrics , Lehigh Valley Health Network , Allentown, Pennsylvania , USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Umaru
authors.affiliation: b Departments of Laboratory Medicine and Pathology , Hematopathology, Mayo Clinic , Rochester, Minnesota , USA.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Swanson
authors.affiliation: b Departments of Laboratory Medicine and Pathology , Hematopathology, Mayo Clinic , Rochester, Minnesota , USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Hoyer
authors.affiliation: b Departments of Laboratory Medicine and Pathology , Hematopathology, Mayo Clinic , Rochester, Minnesota , USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Oliveira
mesh_terms: D019943:Amino Acid Substitution; D000740:Anemia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D003062:Codon; D004252:DNA Mutational Analysis; D005838:Genotype; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000097:blood; D008958:Models, Molecular; D008968:Molecular Conformation; D013163:Splenomegaly; D055544:beta-Globins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D003062:Codon; D006455:Hemoglobins, Abnormal; D055544:beta-Globins
keywords: Double nucleotide substitution; Hb Allentown; Hb S-South End; low oxygen affinity; low oxygen saturation; unstable Hb; variant Hb