Fleming P J, Sumner D R, Wyatt K, Hughes W G, Melrose W D, Jupe D M, Baikie M J
Hematology Department, Institute of Clinical Pathology and Medical Research, Westmead, N.S.W., Australia.
Hemoglobin. 1987;11(3):211-20. doi: 10.3109/03630268709017887.
A new alpha chain hemoglobin variant, Hb Hobart, alpha 20(Bl)His----Arg, was detected in a 60-year-old female of British nationality. The proposita had a history of severe rheumatoid arthritis and had been treated for many years for a refractory microcytic anemia and/or iron deficiency. A hemoglobin electrophoresis screen indicated the presence of a hemoglobin variant, with electrophoretic characteristics similar to a Hb Lepore. However, the level of the variant (17.9%) and the presence of a minor variant Hb A2 band (0.4%) suggested that further investigation was indicated. The variant hemoglobin was purified by column chromatography and the alpha chain subjected to aminoethylation and tryptic digestion. Peptide mapping and amino acid analysis indicated that the histidine residue 20 had been substituted by an arginine residue. The substitution in Hb Hobart is at the first residue in the B Helix of the alpha chain of hemoglobin. As this is an externally placed amino acid in the hemoglobin molecule, a substitution at this position of the hemoglobin molecule would not be expected to cause any functional problems. A family study has shown that at least three other relatives are heterozygous for Hb Hobart. These family members have normal hematological findings.
在一名60岁的英国籍女性中检测到一种新的α链血红蛋白变体，即Hb Hobart，α20(β1)组氨酸突变为精氨酸。该患者有严重类风湿关节炎病史，多年来一直因难治性小细胞贫血和/或缺铁接受治疗。血红蛋白电泳筛查显示存在一种血红蛋白变体，其电泳特征与Hb Lepore相似。然而，该变体的水平（17.9%）以及次要变体Hb A2带的存在（0.4%）表明需要进一步调查。通过柱色谱法纯化变体血红蛋白，并对α链进行氨乙基化和胰蛋白酶消化。肽图谱分析和氨基酸分析表明，第20位的组氨酸残基已被精氨酸残基取代。Hb Hobart中的取代发生在血红蛋白α链β螺旋的第一个残基处。由于这是血红蛋白分子中一个位于外部的氨基酸，预计在该位置的取代不会导致任何功能问题。一项家系研究表明，至少还有其他三名亲属是Hb Hobart的杂合子。这些家庭成员的血液学检查结果正常。
