Hb Tsukumi [beta117(G19)His-->Tyr]: a new hemoglobin variant found in a Japanese male

We accidentally observed an abnormal elution pattern on high performance liquid chromatogram when we examined the Hb A1c level in a 65-year-old male patient who suffered from pneumoconiosis and alcoholic liver injury. The value of the glycated fraction was within the normal range but the elution patterns on high performance liquid chromatography varied with the glycohemoglobin analyzers. Isoelectrofocusing and urea-cellulose column chromatography showed an anomalous fast-moving beta chain estimated at approximately 47%. The instability test of the hemolysate was slightly positive. Structural analysis demonstrated that the mutant was consisted by a substitution of His-Tyr at beta117. This new variant was named Hb Tsukumi for the place of residence of the patient. Additionally, the nucleotide sequence showed a change of C-->T [CAC (His)-->TAC (Tyr)] at the first base in the 117th codon of the beta gene.     

Hb L'Aquila [beta106(G8)Leu-->Val, CTG-->GTG]: a novel thalassemic hemoglobin variant

A new beta-globin variant at codon 106 (CTG-->GTG), and which we named Hb L'Aquila [beta106(G8)Leu-->Val], was detected by DNA analysis. The proband and her father presented with the features of a mild beta(+)-thalassemia (thal), confirmed by their alpha/beta-globin chain biosynthesis ratios.     

Hb south Milwaukee [beta 105 (G7) Leu----Phe]: a newly-identified hemoglobin variant with high oxygen affinity

Fifteen individuals among four generations of a family of English ancestry demonstrated elevated hemoglobin levels accompanied by leftward-shifted whole blood oxygen equilibrium curves. Five of the affected family members have required phlebotomies for relief of symptoms attributable to erythrocytosis. An abnormal hemoglobin or globin chain could not be isolated, but 43% of the beta chains of the affected individuals contained a Leu----Phe substitution at position 105 (G7). Oxygen equilibrium curves demonstrated a normal Bohr effect but decreased cooperativity.     

A new unstable and low oxygen affinity hemoglobin variant: Hb Stanmore [beta 111(G13)Val----Ala

Hb Stanmore is a new hemoglobin variant with the amino acid substitution beta 111(G13)Val----Ala. It is unstable and has a low oxygen affinity. The propositus (of Italian nationality) is a double-heterozygote for Hb Stanmore and beta(0)-thalassemia.     

Hb Matera [beta 55(D6)Met----Lys]: a new unstable hemoglobin variant in an Italian family

Hb Matera is a newly discovered, slow-moving, beta chain variant observed in four members of an Italian family. The variant had a decreased stability in heat and isopropanol tests and numerous red cells contained inclusion bodies. Structural analysis revealed that methionine at position beta 55 was replaced by lysine. Hb Matera's instability is due to an interference in the alpha 1-beta 1 contact of the hemoglobin molecule.     

Hb Johnstown [beta 109 (G11) Val----Leu]: a new electrophoretically silent variant that causes erythrocytosis

A high oxygen affinity hemoglobin, previously undescribed, was found in a healthy, asymptomatic patient with mild erythrocytosis and left-shifted hemoglobin-O2 dissociation curve. The hemoglobin variant could not be distinguished from Hb A by any of several electrophoretic methods nor by ion exchange chromatography. It was separated and analyzed by reversed phase high performance liquid chromatography. Structural analysis revealed the substitution beta 109 (G11) Val----Leu. The variant was named Hb Johnstown. The amino acid substitution perhaps disrupts alpha 1 beta 1 contacts in the deoxyhemoglobin conformation, thus shifting the equilibrium towards the high affinity oxyhemoglobin conformation.