Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO, USA.
Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Hemoglobin. 2020 Jan;44(1):67-69. doi: 10.1080/03630269.2020.1716002. Epub 2020 Jan 27.
A novel unstable γ-globin variant, Hb F-Wentzville [γ24(B6)Gly→Glu; : c.74G>A, (p.Gly25Glu)], was identified in a young infant who required a single transfusion of erythrocytes for hemolytic anemia. This is the first reported γ-globin variant affecting the highly conserved glycine residue at helical position B6. In the tertiary structure of hemoglobin (Hb), glycine at B6 is in close proximity to another invariant glycine residue at E8. Prior studies have shown that replacement of the B6 or E8 glycine residues with bulkier amino acids disrupts packing between the B and E helices, resulting in Hb instability. Thus, Hb F-Wentzville is analogous to the following unstable β-globin B6 variants: Hb Savannah (: c.74G>T, p.Gly24Val), Hb Riverdale-Bronx (: c.73G>C, p.Gly24Arg), and Hb Moscva (: c.74G>A, p.Gly24Asp).
一种新型不稳定的γ-珠蛋白变异体 Hb F-Wentzville [γ24(B6)Gly→Glu; : c.74G>A, (p.Gly25Glu)] 在一名需要输注红细胞以治疗溶血性贫血的年轻婴儿中被鉴定出来。这是第一个报道的影响螺旋位置 B6 高度保守甘氨酸残基的 γ-珠蛋白变异体。在血红蛋白（Hb）的三级结构中，B6 处的甘氨酸与 E8 处的另一个不变甘氨酸残基非常接近。先前的研究表明，用更大的氨基酸取代 B6 或 E8 处的甘氨酸残基会破坏 B 和 E 螺旋之间的堆积，导致 Hb 不稳定。因此，Hb F-Wentzville 类似于以下不稳定的β-珠蛋白 B6 变异体：Hb Savannah [c.74G>T, p.Gly24Val]、Hb Riverdale-Bronx [c.73G>C, p.Gly24Arg] 和 Hb Moscva [c.74G>A, p.Gly24Asp]。
