A novel beta-globin mutation, beta Durham-NC [beta 114 Leu-->Pro], produces a dominant thalassemia-like phenotype.

Journal Article (Journal Article)

Mutations within exon 3 of the beta-globin gene are relatively uncommon, and many of these mutations produce a dominant thalassemia-like phenotype. We describe a novel thalassemic hemoglobinopathy caused by a single nucleotide substitution (CTG-->CCG) at codon 114 resulting in a leucine to proline substitution and designate it beta Durham-NC [beta 114 Leu-->Pro]. The mutation producing this thalassemic hemoglobinopathy is located near to the beta Showa-Yakushiji mutation (beta 110 Leu-->Pro). Both of these hemoglobinopathies share similar phenotypic features with moderately severe microcytic anemia. Using computer imaging of the hemoglobin molecule, we examined several reported point mutations within exon 3 of the beta-globin gene. These point mutations cause a single amino acid substitution in the G helix, and result in a thalassemic and/or hemolytic phenotype. Computer imaging of nine separate examples suggests that amino acid substitutions affecting side chains that project into the heme pocket may destabilize the heme moiety within the beta-globin chain, resulting in a thalassemic phenotype. Hemolytic phenotypes may be the result of decreased alpha 1 beta 1 interactions. The beta Durham-NC mutation further characterizes a novel group of thalassemias/hemoglobinopathies that are clinically difficult to identify and require accessory laboratory testing.

Full Text

Duke Authors

Cited Authors

  • de Castro, CM; Devlin, B; Fleenor, DE; Lee, ME; Kaufman, RE

Published Date

  • February 15, 1994

Published In

Volume / Issue

  • 83 / 4

Start / End Page

  • 1109 - 1116

PubMed ID

  • 8111050

International Standard Serial Number (ISSN)

  • 0006-4971


  • eng

Conference Location

  • United States