Department of Laboratory Medicine, Seoul National University Hospital, 110-744, Seoul, Republic of Korea.
Blood Cells Mol Dis. 2010 Dec 15;45(4):276-9. doi: 10.1016/j.bcmd.2010.10.001. Epub 2010 Oct 29.
Gene fusion is a very rare mechanism that produces hemoglobin variants. Less than ten types of β-like hybrid globins have been reported to date. Herein we identified the first hybrid hemoglobin between Gγ- and β-globins in a five-year-old Korean male who had thalassemia minor feature and triplication of the HBA2 gene (αα/αααα). The novel globin originated from a 27,707-base pair deletion spanning from the HBG2 to HBB gene (NG_000007.3:g.42947_70653del). Its protein sequence included 13 N-terminal amino acids from Gγ-globin, five common amino acids from Gγ- and β-globins, and 128 amino acids from β-globin (Gγ through 13; β from 19). Molecular genetic analyses characterized the hybrid DNA and RNA. Mass spectrometry and de novo protein sequencing successfully identified the fusion peptide in the hybrid hemoglobin. We named this novel hybrid Hb Gγ-β Ulsan. The novel hemoglobin constituted 37.0% of the total hemoglobin and showed reduced oxygen affinity.
基因融合是产生血红蛋白变异体的一种非常罕见的机制。迄今为止，已经报道了不到十种β-样混合球蛋白。在此，我们鉴定了一位 5 岁韩国男性的第一个 Gγ-和β-球蛋白之间的混合血红蛋白，该男性具有轻微地中海贫血和 HBA2 基因（αα/αααα）三倍体。该新的球蛋白源于从 HBG2 到 HBB 基因的 27707 碱基对缺失（NG_000007.3：g.42947_70653del）。其蛋白序列包含 13 个来自 Gγ-球蛋白的 N 端氨基酸、来自 Gγ-和β-球蛋白的 5 个常见氨基酸以及来自β-球蛋白的 128 个氨基酸（Gγ 到 13；β 从 19）。分子遗传学分析对杂种 DNA 和 RNA 进行了特征分析。质谱和从头蛋白质测序成功鉴定了杂种血红蛋白中的融合肽。我们将这种新型混合血红蛋白命名为 Hb Gγ-β Ulsan。新型血红蛋白构成了总血红蛋白的 37.0%，并显示出降低的氧亲和力。
