Structural and functional studies on hemoglobin Bethesda (α2β2145 His), a variant associated with compensatory erythrocytosis

Bunn, H. Franklin; Bradley, Thomas B.; Davis, William E.; Drysdale, James W.; Burke, John F.; Beck, William S.; Laver, Myron B.

doi:10.1172/jci107040

Cited by 43 publications

(20 citation statements)

References 37 publications

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“…This appears to be true for hemoglobin Bethesda (15) and hemoglobin Kempsey (18). The amino acid substitutions in these two variants do not involve 2,3-DPG binding sites.…”

Section: Discussionmentioning

confidence: 88%

Hemoglobin Syracuse (alpha2beta2-143(H21)His leads to Pro), a new high-affinity variant detected by special electrophoretic methods. Observations on the auto-oxidation of normal and variant hemoglobins.

Jensen¹,

Oski²,

Nathan³

et al. 1975

J. Clin. Invest.

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Family members from four generations were found to have polycythemia and increased whole blood 02 affinity (P50; 11 mm Hg; normal, 27 mm Hg). No abnormal hemoglobin bands were seen after electrophoresis on starch gel at pH 8.6 or agar gel at pH 6.0. Analysis of the oxygenated hemolysate by isoelectric focusing on polyacrylamide gel revealed two closely spaced bands. When deoxygenated hemolysate was analyzed in oxygen-free gels, the two components were more widely separated. About 40% of the patient's hemoglobin focused at a more acid pH than hemoglobin A, indicating a hemoglobin variant with impaired Bohr effect. Chromatography of globin in 8 M urea revealed two p-chain peaks, the first of which was eluted at a lower buffer molarity than normal # chain. Fingerprints of tryptic digests of the aminoethylated chains were done on silica gel thin-layer plates. Tp 14 from the abnormal # chain had slower electrophoretic mobility and a greater R. value. Amino acid analyses of this peptide gave values identical with those of j#Tp 14, except that it contained one proline residue and no histidine. Since the one His in #Tp 14 is in position 143, hemoglobin Syracuse is a2PlBHis'PrO. Native Hb Syracuse could be separated from hemoglobin A on a carboxymethylcellulose column. The inclusion of 0.1 mM EDTA in the preparaDr. Jensen was a fellow of the Deutsche Forschungsgemeinshaft.

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“…This appears to be true for hemoglobin Bethesda (15) and hemoglobin Kempsey (18). The amino acid substitutions in these two variants do not involve 2,3-DPG binding sites.…”

Section: Discussionmentioning

confidence: 88%

Hemoglobin Syracuse (alpha2beta2-143(H21)His leads to Pro), a new high-affinity variant detected by special electrophoretic methods. Observations on the auto-oxidation of normal and variant hemoglobins.

Jensen¹,

Oski²,

Nathan³

et al. 1975

J. Clin. Invest.

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“…Approximately 5-mg samples of the purified 8-chain were analyzed for their C-terminal amino acid by hydrazinolysis (12). Purified 8-chains were digested with carboxypeptidase-A (CPA) (13), and the liberated amino acids were quantitated using the Beckman model 121 amino acid analyzer.…”

Section: Methodsmentioning

confidence: 99%

Hemoglobin McKees Rocks (alpha2beta2145Tyr leads to Term). A human "nonsense" mutation leading to a shortened beta-chain.

Winslow¹,

Swenberg²,

Groß³

et al. 1976

J. Clin. Invest.

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“…The reason for the limited number of reported cases with Hb Bethesda is that there are many unclear elements regarding its clinical presentation. The patients with a high oxygen affinity Hb variant, including Hb Bethesda, typically develop secondary erythrocytosis caused by an inappropriate EPO production due to a decrease in the supply of oxygen to tissues (1)(2)(3)(4)(7)(8)(9)(10)(11)(12). In fact, the EPO level in this patient was within the normal range despite a Hct value of 0.61.…”

Section: Discussionmentioning

confidence: 84%

“…The family history of Hb Bethesda presented herein is the eighth such familial case in the world (7)(8)(9)(10)(11)(12)(13). Moreover, it is the second familial case in Japan with the first reported 20 years ago (12).…”

Section: Discussionmentioning

confidence: 99%

A Japanese Family with Congenital Erythrocytosis Caused by Haemoglobin Bethesda

Tamura

Gima

et al. 2015

Intern. Med.

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We herein present a case of congenital erythrocytosis caused by haemoglobin (Hb) Bethesda in a Japanese family. A 55-year-old asymptomatic man was referred to our hospital for the investigation of erythrocytosis, which was present in other members of his family. The patient's serum erythropoietin level was normal, and the JAK2 V617F mutation was not detected. His P50 value was mildly decreased, thus we suspected the presence of an Hb variant with a high oxygen affinity. The high-performance liquid chromatography analysis showed an abnormal Hb, and by direct sequencing we identified the Hb Bethesda variant in this patient. For the differential diagnosis, we recommend the estimation of the P50 value as a practical and useful test.

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Structural and functional studies on hemoglobin Bethesda (α2β2145 His), a variant associated with compensatory erythrocytosis

Cited by 43 publications

References 37 publications

Hemoglobin Syracuse (alpha2beta2-143(H21)His leads to Pro), a new high-affinity variant detected by special electrophoretic methods. Observations on the auto-oxidation of normal and variant hemoglobins.

Hemoglobin Syracuse (alpha2beta2-143(H21)His leads to Pro), a new high-affinity variant detected by special electrophoretic methods. Observations on the auto-oxidation of normal and variant hemoglobins.

Hemoglobin McKees Rocks (alpha2beta2145Tyr leads to Term). A human "nonsense" mutation leading to a shortened beta-chain.

A Japanese Family with Congenital Erythrocytosis Caused by Haemoglobin Bethesda

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