Kaufmann Judith O, Harteveld Cornelis L, Bakker-Verweij Margreet, Arkesteijn Sandra G J, van Delft Peter, Haak Hans, Wijermans Pierre W, Kerkhoffs Jean-Louis, Giordano Piero C
The Reference Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Hemoglobin. 2010;34(1):37-44. doi: 10.3109/03630260903547435.
During a second pilot study, intended to explore the possibility of a country wide implementation of carrier diagnostics for hemoglobinopathies in The Netherlands, we observed a new abnormal hemoglobin (Hb) variant in three members of a family of Scandinavian origin living in the Dutch city of The Hague (Den Haag). The proband, a 34-year-old female presented with low Hb, packed cell volume (PCV) and red blood cell (RBC) values but was normocytic and normochromic. High performance liquid chromatography (HPLC) analysis revealed a partially separated fraction following Hb A. Molecular diagnostics disclosed a TTT>TAT transversion at HBB:c.137 causing a Phe-->Tyr single amino acid substitution at position 45 of the beta-globin gene. Previously described heterozygous mutations at the same position [Hb Cheverly (Phe-->Ser) and Hb Arta (Phe-->Cys)] were reported to be associated with mild chronic hemolysis similar to this case. We describe the hematological features of the six family members, the biochemical and molecular data and we discuss the possible consequences in combination with the common beta-thalassemia (beta-thal) trait.
在第二项试点研究中，旨在探索在荷兰全国范围内实施血红蛋白病携带者诊断的可能性，我们在居住在荷兰海牙市（Den Haag）的一个斯堪的纳维亚血统家庭的三名成员中发现了一种新的异常血红蛋白（Hb）变体。先证者是一名34岁女性，血红蛋白、血细胞比容（PCV）和红细胞（RBC）值较低，但为正细胞正色素性。高效液相色谱（HPLC）分析显示在Hb A之后有一个部分分离的组分。分子诊断显示HBB:c.137处发生TTT>TAT颠换，导致β珠蛋白基因第45位发生Phe→Tyr单氨基酸取代。先前报道在同一位置的杂合突变[Hb Cheverly（Phe→Ser）和Hb Arta（Phe→Cys）]与类似于此病例的轻度慢性溶血有关。我们描述了这六名家庭成员的血液学特征、生化和分子数据，并结合常见的β地中海贫血（β-地贫）特征讨论了可能的后果。
