Haemoglobin G Norfolk α 85 (F6) Asp → Asn. Structural characterization by sequenator analysis and functional properties of a new variant with high oxygen affinity

Abstract The functional properties and primary structure of a new β-chain mutant of human hemoglobin are described. The mutant was transmitted as an autosomal dominant characteristic. Affected members of the kindred exhibited marked erythrocytosis due to the high oxygen affinity of the resultant hemoglobin. The abnormality is associated with a substitution of an asparaginyl residue for lysine in the 144 position of the β-chain, αA2β144Lys→Asn2, presumably due to an AAA/G to AAA/U transversion. The mutant hemoglobin displayed a profound increase in oxygen affinity, with a P50 of the fresh whole blood of 14 mm Hg. The isolated mutant hemoglobin exhibited near normal heme—heme interaction, a half-normal Bohr effect, and normal reactivity with 2,3-diphosphoglycerate.

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Structure-Function Relationships in Hemoglobin Kariya, Lys-40(C5)α → Glu, with High Oxygen Affinity

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)60445-4 ◽

1989 ◽

Vol 264 (19) ◽

pp. 11174-11180

Author(s):

K Imai ◽

A Tsuneshige ◽

T Harano ◽

K Harano

Keyword(s):

Structure Function ◽

Oxygen Affinity ◽

High Oxygen ◽

High Oxygen Affinity

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Hemoglobin fort gordon or α2β2145 Tyr → Asp, a new high-oxygen-affinity hemoglobin variant

Biochimica et Biophysica Acta (BBA) - Protein Structure ◽

10.1016/0005-2795(75)90189-0 ◽

1975 ◽

Vol 400 (2) ◽

pp. 343-347 ◽

Cited By ~ 26

Author(s):

H.B. Kleckner ◽

J.B. Wilson ◽

J.G. Lindeman ◽

P.D. Stevens ◽

G. Niazi ◽

...

Keyword(s):

Oxygen Affinity ◽

High Oxygen ◽

Hemoglobin Variant ◽

High Oxygen Affinity

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Unusual finding of high oxygen affinity haemoglobinopathy treated with phlebotomy: a rare but predictable union

Transfusion and Apheresis Science ◽

10.1016/j.transci.2021.103290 ◽

2021 ◽

pp. 103290

Author(s):

Epifania Rita Testa ◽

Adriana Masotti ◽

Patrizia Valeri ◽

Luciana Geremia ◽

Valeria Brunetta ◽

...

Keyword(s):

Oxygen Affinity ◽

High Oxygen ◽

High Oxygen Affinity ◽

Unusual Finding

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Haemoglobin Olympia {β Codon 20 (B2) G→A, Val→Met}: A Silent Haemoglobin Variant

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/47560.14677 ◽

2021 ◽

Author(s):

Abhay A Bhave ◽

Lakshmi Iyer ◽

Nawal Kazi ◽

Manju Gorivale ◽

Anita Nadkarni

Keyword(s):

High Performance ◽

Extended Family ◽

Globin Gene ◽

Oxygen Affinity ◽

High Oxygen ◽

Cerebral Vessel ◽

Haemoglobin Variant ◽

First Case ◽

History Of ◽

High Oxygen Affinity

High oxygen affinity haemoglobin variants are rare and often underdiagnosed in persistent erythrocytosis with no apparent aetiology. Here the author present a 29-year-old Indian male patient with a long-standing history of erythrocytosis which was incidentally detected. The proband had a prothrombotic family history of cerebral vessel stroke in his paternal grandfather at a young age and unexplained erythrocytosis in his father and brother. A review of his haemograms showed persistent high haemoglobin values. Routine tests did not reveal any specific aetiology and haemoglobin electrophoresis by High-Performance Liquid Chromatography (HPLC) showed absence of any abnormal peak or unstable haemoglobin. DNA sequencing of the β globin gene revealed heterozygosity for codon 20 {GTG→ATG, Valine (Val)→ Methionine (Met)} mutation confirming the presence of an electrophoretically silent Hb variant - Haemoglobin Olympia in him and his extended family members. This case study emphasises importance of this rare entity of high oxygen affinity haemoglobin variant as a differential diagnosis while screening for erythrocytosis. This is the first case report of Haemoglobin Olympia from India reported in the literature.

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