台灣首度發現的血色素Lepore：一種同時具有乙型海洋性貧血特徵的血色素Lepore-Boston-Washington

The First Hb Lepore found in Taiwan: a β-thalassemic Hb Lepore-Boston-Washington

這次台大醫院首次發現的變異血色素Hb Lepore-Boston-Washington (Hb Lepore-BW) 已經在許多地區被報告過。Hb Lepore-Boston-Washington (Hb Lepore-BW; δ87-β116)是一種δβ融合基因的變異，臨床症狀與乙型海洋性貧血相同。本實驗室使用了高效率液體層析儀(high-performance liquidchromatography; HPLC；Bio-Rad D10)、毛細管電泳 (capillary electrophoresis; CE；SEBIAMinicap)、GAP PCR以及Sanger’s直接定序核酸序列。Hb Lepore-BW在D10 HPLC的位置與Hb A2很接近，無法與Hb A2區分，而形成兩個融合的波形。Hb Lepore-BW在Sebia Minicap毛細管電泳的位置在Hb F與Hb S之間(Z6:200~220)。直接基因定序結果顯示δ基因與β基因有一段58bp的重疊，其5'端為δ的第87個胺基酸位置，3'端為β的第二個intron第8個位置；符合Hb Lepore-BW的基因變異。這個變異在台灣是首次被發現的，HLA genotyping分析結果顯示此病人沒有特殊族群的背景。因為此變異與乙型海洋性貧血的臨床表現類似，因此其在臨床檢驗室的診斷是非常重要的。

Hemoglobin Lepore-Boston-Washington has a worldwide distribution in many different ethnic groups. Hb Lepore-Boston-Washington (Hb Lepore-BW; δ87-β116) is composed of two δβ fusion globin and two α globin chains, which clinically manifests similar to a phenotype of β+-thalassemia. In this study, HPLC (high-performance liquid chromatography; HPLC; Bio-Rad D10), capillary electrophoresis (capillary electrophoresis; CE; SEBIA Minicap), GAP PCR and Sanger's direct sequencing were used and identified an unknown Hb variant. We demonstrated that this Hb variant located closely to the position of Hb A2 in D10 HPLC system and located between Hb F and Hb S (Z6: 200 ~ 220) in Sebia Minicap capillary electrophoresis analysis. Direct sequencing showed a fragment composed of the 5 'end of the δ87 and the 3' end of the βIVS-II-8 with a crossover region of 58bp shared by δ globin and the β globin genes, compatible with the δβ fusion gene variation of Hb Lepore-BW. This variation was first found in Taiwan and further HLA genotyping analysis showed this patient without any special ethnic background. Due to the clinical significance of Hb Lepore-BW is similar to the β-thalassemia; the laboratory diagnosis of this Hb Lepore is of importance.