瑞士一个家族中发现一种具有增高氧亲和力的新型α-珠蛋白变异体：弗劳恩费尔德血红蛋白[α138(H21)丝氨酸→苯丙氨酸，TCC>TTC(α2)]

A new alpha-globin variant with increased oxygen affinity in a Swiss family: Hb Frauenfeld [alpha 138(H21)Ser-->Phe, TCC>TTC (alpha 2)].

作者信息

Hochuli Michel, Zurbriggen Karin, Schmid Marlis, Speer Oliver, Rochat Philippe, Frauchiger Beat, Kleinert Peter, Schmugge Markus, Troxler Heinz

机构信息

Department of Internal Medicine, Kantonsspital Frauenfeld, Frauenfeld, Switzerland.

出版信息

Hemoglobin. 2009;33(1):54-8. doi: 10.1080/03630260802625733.

DOI:10.1080/03630260802625733

PMID:19205974

Abstract

A new alpha-globin mutation [alpha 138(H21)Ser-->Phe] was found in a 55-year-old male proband with an erythrocytosis known since his youth. Cation exchange high performance liquid chromatography (HPLC) revealed an additional peak eluting slightly before Hb A indicating the presence of a variant. The peak area of the variant was approximately one-third that of Hb A suggesting an alpha-globin variant. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis confirmed the mutation at the protein level. The variant is also detectable with isoelectric focusing and reversed phase HPLC. DNA analysis revealed a heterozygous sequence mutation at codon 138 of the alpha2 gene. A C>T transition at the second nucleotide of the codon indicated a Ser-->Phe exchange. The variant showed increased oxygen affinity and was named Hb Frauenfeld.

摘要

在一名55岁的男性先证者中发现了一种新的α-珠蛋白突变[α138(H21)Ser→Phe]，该先证者自幼就患有红细胞增多症。阳离子交换高效液相色谱法（HPLC）显示，在Hb A之前有一个额外的峰洗脱出来，表明存在一种变体。该变体的峰面积约为Hb A的三分之一，提示为α-珠蛋白变体。基质辅助激光解吸电离飞行时间质谱分析在蛋白质水平证实了该突变。该变体也可用等电聚焦和反相HPLC检测到。DNA分析显示α2基因第138密码子处存在杂合序列突变。密码子第二个核苷酸处的C>T转换表明发生了Ser→Phe交换。该变体显示出增加的氧亲和力，被命名为Hb Frauenfeld。