Hemoglobin S/hemoglobin Osler: a case with 3 beta globin chains. DNA sequence (AAT) proves that Hb Osler is beta 145 Tyr-->Asn

Am J Hematol. 1996 Aug;52(4):305-9. doi: 10.1002/(SICI)1096-8652(199608)52:4<305::AID-AJH10>3.0.CO;2-C.

Abstract

A 13-year-old African-American female with erythrocytosis and three different beta globins on electrophoresis beta A, beta S, and beta Osler, raised the possibility that one chromosome 11 might contain a duplicated beta globin gene, since there are normally only 2 beta globin genes. DNA sequence analysis showed GTG at codon 6 in exon 1, corresponding to Hb S and AAT at codon 145 in exon 3, indicating a substitution of Asn for Tyr. Thus, Hb Osler undergoes spontaneous post-translational deamidation, beta 145 Asn-->beta 145 Asp. Unmodified Hb Osler (Asn) co-migrates with Hb A on electrophoresis and co-elutes with Hb A on HPLC; therefore it has not been identified previously. All previous studies have incorrectly identified the mutation as being beta 145 (HC 2) Tyr-->Asp.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Base Sequence
  • Chromosomes, Human, Pair 11
  • DNA / chemistry*
  • Exons
  • Female
  • Globins / genetics*
  • Hemoglobin, Sickle / genetics*
  • Hemoglobins, Abnormal / genetics*
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Sequence Analysis, DNA
  • Twins, Dizygotic

Substances

  • Hemoglobin, Sickle
  • Hemoglobins, Abnormal
  • hemoglobin Osler
  • Globins
  • DNA