Blanke S, Johnsen A, Wimberley P D, Mortensen H B
Department of Clinical Chemistry, Rigshospitalet, University of Copenhagen, Denmark.
Biochim Biophys Acta. 1988 Jul 20;955(2):214-9. doi: 10.1016/0167-4838(88)90195-1.
Isoelectric focusing of hemolysate from patients with diabetes mellitus is routinely performed to measure their level of HbA1c (glycated hemoglobin). For a 6 year old boy with diabetes mellitus this analysis showed an HbA1c fraction of approx. 50%, which is very unlikely to occur. The possibility of a hemoglobin variant was considered, and by HPLC-separation the presence of two different beta-chains was shown. One tryptic fragment was found to deviate from the normal, and amino-acid analysis and sequence determination revealed the following amino-acid substitution: beta 116 His----Gln. It is the first reported mutation at this position. Functional studies showed almost normal behaviour, consistent with the fact that the affected persons are without any symptoms. In a family survey we found five nondiabetic members with an abnormality similar to the proband. For the variant we chose the name Hafnia, which is Latin for Copenhagen.
常规对糖尿病患者的溶血产物进行等电聚焦，以测量其糖化血红蛋白（HbA1c）水平。对于一名6岁糖尿病男孩，该分析显示HbA1c比例约为50%，这极不可能出现。考虑到存在血红蛋白变异体的可能性，通过高效液相色谱分离显示存在两条不同的β链。发现一个胰蛋白酶片段与正常情况不同，氨基酸分析和序列测定揭示了以下氨基酸取代：β116位组氨酸突变为谷氨酰胺。这是该位置首次报道的突变。功能研究显示其行为几乎正常，这与患者没有任何症状的事实相符。在家族调查中，我们发现五名非糖尿病家庭成员存在与先证者相似的异常情况。我们将该变异体命名为哈夫尼亚（Hafnia），在拉丁语中意为哥本哈根。
