血红蛋白克里特（β129丙氨酸突变为脯氨酸）：一种与β0和δβ0地中海贫血相互作用的新型高亲和力变体。

Hemoglobin Crete (beta 129 ala leads to pro): a new high-affinity variant interacting with beta o -and delta beta o -thalassemia.

作者信息

Maniatis A, Bousios T, Nagel R L, Balazs T, Ueda Y, Bookchin R M, Maniatis G M

出版信息

Blood. 1979 Jul;54(1):54-63.

Abstract

Hemoglobin Crete, beta129 (h7)ala leads to pro, is a new mutant hemoglobin (Hb) with high oxygen affinity that was discovered in a Greek family in various combinations with beta- and deltabeta-thalassemia. The propositus, who presented an unusual clinical picture of an "overcompensated" hemolytic state, with erythrocytosis, splenomegaly, abnormal red cell morphology, and marked erythroid hyperplasia, appeared doubly heterozygous for Hb Crete and deltabeta-thalassemia. His red cells contained 67% Hb Crete and 30% Hb F, and the combination of these two hemoglobins resulted in a blood P50O2 of 11.2 mm Hg. A brother with Hb Crete trait (38% Hb Crete, 56% Hb A, blood P50O2 23.0 mm Hg) did not have significant erythrocytosis. Purified Hb Crete was heat-unstable and exhibited a high oxygen affinity, and a normal Bohr effect. We postulate that the beta 129 proline substitution disrupts the H helix, perturbing nearby residues involved in alpha 1 beta 1 contact sites of the Hb tetramer.

摘要

血红蛋白克里特，β129（h7）丙氨酸突变为脯氨酸，是一种新的具有高氧亲和力的突变血红蛋白（Hb），在一个希腊家族中被发现，它与β-和δβ-地中海贫血有多种组合形式。先证者表现出一种不寻常的“过度代偿”溶血性状态的临床症状，有红细胞增多、脾肿大、异常红细胞形态以及明显的红系增生，似乎是血红蛋白克里特和δβ-地中海贫血的双重杂合子。他的红细胞含有67%的血红蛋白克里特和30%的血红蛋白F，这两种血红蛋白的组合导致血液P50O2为11.2毫米汞柱。一名具有血红蛋白克里特特征（38%血红蛋白克里特，56%血红蛋白A，血液P50O2 23.0毫米汞柱）的兄弟没有明显的红细胞增多。纯化的血红蛋白克里特热不稳定，表现出高氧亲和力和正常的玻尔效应。我们推测β129脯氨酸替代破坏了H螺旋，扰乱了参与血红蛋白四聚体α1β1接触位点的附近残基。