HB Ube-2 (α68[E-17]ASN→ASP): The Second Instance in Japan

Iuchi, I; Shimasaki, Shunichi; Hidaka, Kazuo; Ueda, Seinosuke; Shibata, Susumu; Mizushima, Jun

doi:10.3109/03630268108991691

Cited by 6 publications

(4 citation statements)

References 11 publications

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“…few cases have been reported in the literature (7)(8)(9), probably becauseof the minimaleffect of this abnormalHbon hematological functions. Indeed, an instability test of the Hbwas negative and nohematologicalsymptoms weresubjectively registered in the present case.…”

Section: Discussionmentioning

confidence: 99%

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Hb Ube-2 in a Diabetic Case with an Abnormally Low HbA1C Value.

Hamaguchi

Harano

et al. 1999

Intern. Med.

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A 69-year-old male diabetic patient had an abnormally low HbAlc value of 2.8% , which was inconsistent with his elevated fasting plasma glucose of 8.2 mmol//. Hb analysis disclosed that the abnormal Hb was Hb Ube-2 [oc68 (E17) Asn -+ Asp] and it accounted for 21.5% of the total Hb. Since the glycated abnormal Hb emerged at the same position as did HbF on high performance liquid chromatography, the HbAlc value was falsely low. The present case demonstrates that Hb Ube-2 is one of the abnormal Hbs in which caution should be exercised when monitoring diabetic control. (Internal Medicine 38: 800-803, 1999)

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Section: Discussionmentioning

confidence: 99%

“…Hb Ube-2 has not been extensively described because of its minimal effect on hematological functions (7,9). It has not been previously reported in relation to abnormal HbAlc level in diabetic patients.…”

Section: Introductionmentioning

confidence: 99%

Hb Ube-2 in a Diabetic Case with an Abnormally Low HbA1C Value.

Hamaguchi

Harano

et al. 1999

Intern. Med.

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“…For example, amino acid substitutions located at α 68(E17) position such as in HbUbe ( α 2 68Asn→ Asp β 2 ) [12, 13] do not influence the functional properties of Hb molecule, while for HbG-Philadelphia two previous papers proposed opposite results [14, 15]: North et al [14] reported an increased oxygen affinity not detected by Pardoll et al [15]. HbDuarte has an oxygen affinity higher than the HbA and a moderate instability [9, 11].…”

Section: Introductionmentioning

confidence: 99%

Structural and Functional Characterization of a New Double Variant Haemoglobin (HbG-Philadelphia/Duarteα268Asn→Lysβ262Ala

et al. 2011

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We report the first case of cosegregation of two haemoglobins (Hbs): HbG-Philadelphia [α68(E17)Asn → Lys] and HbDuarte [β62(E6)Ala → Pro]. The proband is a young patient heterozygous also for β°-thalassaemia. We detected exclusively two haemoglobin variants: HbDuarte and HbG-Philadelphia/Duarte. Functional study of the new double variant HbG-Philadelphia/Duarte exhibited an increase in oxygen affinity, with a slight decrease of cooperativity and Bohr effect. This functional behaviour is attributed to β62Ala → Pro instead of α68Asn → Lys substitution. Indeed, HbG-Philadelphia isolated in our laboratory from blood cells donor carrier for this variant is not affected by any functional modification, whereas purified Hb Duarte showed functional properties very similar to the double variant. NMR and MD simulation studies confirmed that the presence of Pro instead of Ala at the β62 position produces displacement of the E helix and modifications of the tertiary structure. The substitution α68(E17)Asn → Lys does not cause significant structural and dynamical modifications of the protein. A possible structure-based rational of substitution effects is suggested.

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“…Hb Ube-2 [α68 (E17) Asn→Asp] was originally observed in a Japanese individual in 1967 (6). To our knowledge, it has only ever been observed in the Japanese and Taiwanese population (7).…”

Section: Introductionmentioning

confidence: 99%

Molecular characteristics of three hemoglobin variants observed in a Chinese population: Hb Ube-1 [β98 (FG5) Val→Met], Hbï¿½Ube‑2 [α68 (E17) Asn→Asp] and Hbï¿½Ube‑4 [α116 (GH4) Glu→Ala]

Huang

Lin

et al. 2011

Mol Med Report

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Abstract. In this study we report three cases of Hb Ube-1, one case of Hb Ube-2 and one case of Hb Ube-4 in mainland China. One case of Hb Ube-1 had the clinical manifestation of hemolytic anemia. Hb Ube-2 and Hb Ube-4 did not appear to be associated with clinical or hematological abnormalities. The variants were detected by Hb electrophoresis during a thalassemia screening. Genomic DNA was extracted from the peripheral blood leukocytes of Hb specimens. α1, α2 and β-globin genes were amplified by polymerase chain reaction (PCR). All variants were confirmed by DNA sequence analysis and the PCR-restriction fragment length polymorphism assay. IntroductionA recent query of the Human Hemoglobin Variant database (HbVar) (http://globin.cse.psu.edu) identified 652 variants of the α-globin chain and 775 variants of the β-globin chain. The majority of these hemoglobin variants do not have any hematological or clinical effects and are often found incidentally, for example during newborn screening or health examination, and are finally identified by DNA sequencing.Hb Ube-1 [β98 (FG5) Val→Met], also known as Hb Koln, was first observed in Cologne, Germany, by Pribilla in 1965. It is often found in Europe and America, and has occasionally been reported in Japan, South Korea and Taiwan (1-3). Hb Ube-1, in which the β98 (FG5) valine residue is replaced by methionine (G→A), is the most frequent unstable hemoglobin. However, it presents very few features that allow its distinction from other unstable hemoglobin variants. Mild anemia, jaundice and persistent excretion of dark urine characterize the clinical manifestations of Hb Ube-1. The relationship between the amino acid substitution (Val→Met) and the instability of this hemoglobin suggests that the valine residue is in contact with the heme in the normal β-chain. The substitution of valine for methionine changes the steric configuration of the β-globin, which either alters the enzymatic reduction of iron or results in an increased conversion of meta-hemoglobin into denatured hemoglobin. When Hb Ube-1 is in the oxygenated conformation, the molecule is saturated with heme groups and is stable. The transition to the deoxygenated state results in the loss of heme groups, the instability of Hb and the precipitation and formation of Heinz bodies, which are cytoplasmic degradation products attached to the cell membrane (4). Heinz bodies induce hemolysis and splenomegaly (5).Hb Ube-2 [α68 (E17) Asn→Asp] was originally observed in a Japanese individual in 1967 (6). To our knowledge, it has only ever been observed in the Japanese and Taiwanese population (7). This Hb variant resulted from an AAC→GAC mutation at codon 68 of the α-globin gene. Hb Ube-2 carriers do not have clinical symptoms or hematological changes, and their oxygen affinity is normal.Hb Ube-4 [α116 (GH4) Glu→Ala (α1)] is an abnormal hemoglobin, that was first observed in a Korean family residing in Japan (8). To the best of our knowledge, all Hb Ube-4 carriers have been found in Korea or Japan (9). This hemoglobin varian...

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HB Ube-2 (α68[E-17]ASN→ASP): The Second Instance in Japan

Cited by 6 publications

References 11 publications

Hb Ube-2 in a Diabetic Case with an Abnormally Low HbA1C Value.

Hb Ube-2 in a Diabetic Case with an Abnormally Low HbA1C Value.

Structural and Functional Characterization of a New Double Variant Haemoglobin (HbG-Philadelphia/Duarteα268Asn→Lysβ262Ala

Molecular characteristics of three hemoglobin variants observed in a Chinese population: Hb Ube-1 [β98 (FG5) Val→Met], Hbï¿½Ube‑2 [α68 (E17) Asn→Asp] and Hbï¿½Ube‑4 [α116 (GH4) Glu→Ala]

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