A novel beta-globin mutation, beta Durham-NC [beta 114 Leu-->Pro],
produces a dominant thalassemia-like phenotype
CM de Castro, B Devlin, DE Fleenor, ME Lee and RE Kaufman
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
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.
Volume 83,
Issue 4,
pp. 1109-1116,
02/15/1994
Copyright © 1994 by The American Society of Hematology
