Hb KODAIRA II: A HIGH OXYGEN AFFINITY VARIANT WITH A NOVEL MUTATION IN THEβ-GLOBIN GENE AND PHENOTYPIC IDENTITY TO Hb KODAIRA

Abstract

A 35-year-old lady with a history of good health was diagnosed as having impaired glucose tolerance during pregnancy. A hemoglobin (Hb) variant was incidentally detected when her blood was assayed for Hb A 1c by automatic cation exchange high performance liquid chromatography (HPLC). Peripheral blood examination showed mild polycythemia: Hb 15.5 g=dL (normal 11.7-14.9 g=dL), RBC 5.57610 12 =L (normal 3.9-5.0610 12 =L), PCV 0.46 L=L (normal 0.35-0.45 L=L), MCV 82.7 fL (normal 82-97 fL), MCH 27.7 pg (normal 27-33 pg) and MCHC 33.5 g=dL (normal 32-35 g=dL), with normal red cell morphology. Hb analysis using HPLC showed 45.8% Hb A, 2.7% Hb A 2 (normal 1.5-3.5%) and a slightly increased Hb F value of 1.6% (normal <1%) which was probably related to her pregnant state. The rest (49.9%) was made up of a Hb variant. The variant co-migrated with Hb A in cellulose acetate electrophoresis at pH 8.3, but was separable from the latter at pH 6.0 (Fig. 1). Globin chain electrophoresis at pH 8.8 showed that it was probably a b chain variant (data not shown).The raised Hb level, normal red cell morphology and absence of clinical symptoms of anemia were suggestive of a Hb variant with high oxygen affinity. DNA sequencing of the b-globin gene revealed that the patient was heterozygous * Corresponding

Hb Niigata [β1(Na1)Val→Leu] in a Romanian Individual Resulting from Another Nucleotide Substitution than that Found in the Japanese

“…This situation has been observed for a few other β Hb mutations. Some examples are Hb Kodaira [β146(HC3)His→Gln], which may be produced by two different point mutations; (CAC→CAA or CAG) (12,13) and the nonsense codon at position 15 (TGG→TGA) leading to a β 0 -thalassemia (thal) (14,15). Thus, identical gene products may result from different genotypes.…”