Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Int J Lab Hematol. 2012 Oct;34(5):551-5. doi: 10.1111/j.1751-553X.2012.01424.x. Epub 2012 Apr 11.
To report a new hemoglobin variant undistinguishable from the common HbS on HPLC. To show the efficiency of the simplest confirmation method for HbS and to discuss the implications that may occur if HbS-like variants are wrongly reported as HbS.
Basic hematology, separation and measurement of the Hb fractions, 'sickle test,' and molecular analysis.
The abnormal Hb fractions were eluting in the HbS window on HPLC, sickle test was however negative, and DNA sequencing of the beta globin gene revealed an unclassified variant HBBc.23A>T, p.Glu8Val in heterozygous form.
Although the amino acid substitution of this new variant is identical to that of HbS and shifted of a single amino acid position, no polymerization occurs in vitro. The sickle test is a valid method to confirm or exclude HbS trait in individual cases. Whenever the case is part of a possible couple at risk, then one has to use full DNA analysis in both partners not to miss hidden concomitant defects important for genetic risk predictions.
报告一种与 HPLC 上常见的 HbS 无法区分的新型血红蛋白变异体。展示用于确认 HbS 的最简单方法的效率，并讨论如果将类似 HbS 的变异体错误报告为 HbS 可能产生的影响。
基础血液学、Hb 分数的分离和测量、镰状细胞检测以及分子分析。
异常的 Hb 分数在 HPLC 上的 HbS 窗口中洗脱，但镰状细胞检测呈阴性，β珠蛋白基因的 DNA 测序显示存在一种未分类的变异体 HBBc.23A>T，p.Glu8Val 为杂合形式。
尽管这种新型变异体的氨基酸取代与 HbS 相同，且只发生了一个氨基酸位置的改变，但体外不会发生聚合。镰状细胞检测是确认或排除个体 HbS 特征的有效方法。但如果该病例是有潜在风险的夫妇的一部分，那么就必须在双方中使用完整的 DNA 分析，以避免错过对遗传风险预测至关重要的隐藏伴随缺陷。
