Hb Adana or alpha 2(59)(E8)Gly-->Asp beta 2, a severely unstable alpha 1-globin variant, observed in combination with the -(alpha)20.5 Kb alpha-thal-1 deletion in two Turkish patients.
We have identified a severely unstable hemoglobin variant through sequencing of amplified DNA involving the alpha 1-globin gene; the mutation is located in codon 59 (CCG CAG) and results in a Gly-->Asp replacement. This amino acid substitution concerns a glycine residue at an internal position in the E helix, which is in close contact with a glycine residue of the B helix; introduction of the larger and charged aspartic acid residue greatly affects the stability of the molecule. This variant was present in association with a common alpha-thalassemia-1 deletion [-(alpha)20.5 kb] in two adults and caused a severe type of Hb H disease with anemia, low levels of Hb A2, increased zeta chain, and Hb Bart's. In vitro chain synthesis in reticulocytes showed a high specific activity of the variant alpha chain. Only a minute quantity of Hb H was present but instead about 10% of Hb Bart's was observed. The increased synthesis of gamma chains was likely due to specific characteristics of a chromosome with haplotype #3, which was present in both patients. The same family was studied 18 years ago; the improved methodology presently available has led to a corrected diagnosis for these patients.
Cürük
M A
MA
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
Dimovski
A J
AJ
Baysal
E
E
Gu
L H
LH
Kutlar
F
F
Molchanova
T P
TP
Webber
B B
BB
Altay
C
C
Gürgey
A
A
Huisman
T H
TH
D000328:Adult; D000595:Amino Acid Sequence; D001224:Aspartic Acid; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D005914:Globins / Q000235:genetics*; D005998:Glycine; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D017354:Point Mutation; D012156:Reticulocytes / Q000378:metabolism; D017384:Sequence Deletion; D014421:Turkey / Q000208:ethnology; D017085:alpha-Thalassemia / Q000097:blood / Q000235:genetics*
D006455:Hemoglobins, Abnormal; D015345:Oligonucleotide Probes; C083925:hemoglobin Adana; D001224:Aspartic Acid; D005914:Globins; D005998:Glycine