T A B L E 2 8 -5
Molecular and Clinical Characteristics of Some Abnormal Hemoglobins
Amino Acid
DNA Codon'
Hemoglobin
Position*
Change
Alterations
Remarks*
a-Globin Mutations
Memphis
23(B4)
Glu—»Gin
GAG—»CAG
Torino
43(CEI)
Phe—»Val
TTC—»GTC
Ann Arbor
80(F1)
Leu—»Arg
CTG-aCGG
Chesapeake
92(FG4)
Arg—»Leu
CGG—»CTG
G-Georgia
95(G2)
Pro—»Leu
CCG—»CTG
Bibba
■Globin Mutations
136(H19)
Leu—»Pro
CTG-aCCG
S
6(A3)
Glu—»Val
GAG—»GTG
G-Makassar
6(A3)
Glu—»Ala
GAG—»GCG
C
6(A3)
Glu—»Lys
GAG—»AAG
Leiden
6
or 7
(A3 or 4)
Glu—»—
GAG-»—
G-San Jose
7(A4)
Glu—»Gly
GAG^GCG
Saki
14(A11)
Leu—»Pro
CTG—»CCG
Savannah
24(B6)
Gly^Val
GGT-aGTT
E
26(B8)
Glu—»Ljs
GAG^AAG
Genova
28(B10)
Leu—»Pro
CTG-aCCG
St. Louis
28(B10)
Leu—»Gin
CTG—»CAG
Tacoma
30(B12)
Arg—»Ser
AGG—»AG(T,C)
Abraham Lincoln
32(B14)
Leu—»Pro
CTG^CCG
Philly
35(CI)
Tyr—»Phe
TAC-»TTC
Hammersmith
42(CD1)
Phe—»Ser
TTT—»TCT
Louisville
42(CD1)
Phe—»Leu
TTT—»TT(A,G)
or TTC
Tochigi
56-59
(D7-E3)
deletion
—
Bristol
67(E11)
Val-»Asp
GTG—»GA(T,G)
Sydney
67 (E11)
Val^Ala
GTG—»GGG
Seattle
70(E14)
Ala—»Asp
GCC^GAC
Shepherd’s Bush
74(E18)
Gly—»Asp
GGC^GAC
Tours
87(F3)
Thr-A—
ACA-a—
Gun Hill
91-95
deletion
—
Koln
98(FG5)
Val-AMet
GTG—»ATG
Nottingham
98(FG5)
Val—»Gly
GTG^GGG
Kempsey
99(G1)
Asp—»Asn
GAT-aAAT
Reduces sickling when present in HbS homozygotes.
Decreases 0
2
affinity; unstable; mild anemia;
decreases heme binding.
Unstable.
Increases 0
2
affinity; R state stabilized;
al
/32-contact mutant.
Oxy form dissociates to dimers; decreases 0
2
affinity;
a, j32-contact mutant.
Dissociates.
See discussion of sickle cell anemia in this chapter
Benign; does not interact with HbS.
Crystallizes in red blood cells; enhances sickling
when heterozygous with HbS.
Deletion decreases 0
2
affinity; mild hemolysis;
unstable.
Compare to HBS; benign.
Unstable; Pro disrupts a-helix.
Unstable.
Mild hemolytic anemia; increases subunit
dissociation; normal
0 2
affinity; a j /3j -contact
mutant
Increases 0
2
affinity; unstable.
Iron readily oxidized; polar group in heme pocket;
increases
0 2
affinity; unstable.
Normal 0
2
affinity; decreases Bohr effect; unstable.
Also called Perth; unstable.
Loss of H bond needed to stabilize T state; high 0
2
affinity; unstable.
Decreases 0
2
affinity; unstable; poor heme binding
severe anemia; inclusion bodies.
Decreases 0
2
affinity; unstable; mild anemia; heme
misoriented but not lost.
Shortening of E-helix; unstable.
Unstable; polar group in heme pocket; unusual
codon needing
2
mutations.
Unstable; mild hemolysis; inclusion bodies; poor
heme binding.
Unstable; mild hemolysis; decreases 0
2
affinity.
Unstable; increases 0
2
affinity; negative charge in
DPG site; decreases DPG binding.
Deletion shortens F-helix; unstable; increases 0
2
affinity.
Deletion shortens F-helix; unstable; increases 0
2
affinity.
Unstable; increases 0
2
affinity; oCjj32-contact mutant.
Unstable; increases 0
2
affinity; T-state destabilized.
Increases 0
2
affinity; R-state stabilized.
(continued)
