Hemoglobin S/hemoglobin Osler: a case with 3 beta globin chains. DNA sequence (AAT) proves that Hb Osler is beta 145 Tyr-->Asn.
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.
Hutt
P J
PJ
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Donaldson
M H
MH
Khatri
J
J
Fairbanks
V F
VF
Hoyer
J D
JD
Thibodeau
S N
SN
Moxness
M S
MS
McMorrow
L E
LE
Green
M M
MM
Jones
R T
RT
D000293:Adolescent; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D004247:DNA / Q000737:chemistry*; D005091:Exons; D005260:Female; D005914:Globins / Q000235:genetics*; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA; D014429:Twins, Dizygotic
D006451:Hemoglobin, Sickle; D006455:Hemoglobins, Abnormal; C036601:hemoglobin Osler; D005914:Globins; D004247:DNA