Two familial cases of Hb Tyne confirm instability as cause of low expression

Abstract

We report a second occurrence of hemoglobin (Hb) Tyne, [β5 (A2) Pro>Ser] HBB :c.16C>T(p.Pro6Ser), which like the first case was associated with normal hematology. We verified the variant was mildly unstable by showing it was greatly enriched in isopropanol precipitates. This minor instability accounts for the slightly decreased expression of the new β chain. The variant was picked up as an interfering component on HbA1c testing using cation exchange high performance liquid chromatography (HPLC). However, this may be an advantage in detecting electrophoretically silent variants. Furthermore, this report also highlights the importance of uneven or sloping baselines on HPLC, which could reflect the presence of a variant hemoglobin even in the presence of normal electrophoresis and full blood count. 我们报告了第二例血红蛋白(Hb) Tyne [β5 (A2) Pro>Ser] HBB:c.16C>T(p.Pro6Ser)的出现，其与第一例一样伴随血象正常。我们通过将该变体在异丙醇沉淀物中的显著富集证实了其有轻度不稳定性。这种微小的不稳定性可用来说明新β链表达的轻微下降。该变体在使用阳离子交换高效液相色谱（HPLC）的HbA1c检测中作为干扰成分检出。然而，在检测电泳沉默变体方面这可能使一个优势。此外，本报告还强调了不平或倾斜的基线对HPLC的重要性，这会反映出血红蛋白变异体的存在，即使电泳和全血计数正常。