β-地中海贫血(β-thal)是由β-珠蛋白基因突变引起的,导致血红蛋白(Hb)β链的合成减少(β)或缺乏(β0)。在这份报告中,一名28岁的男性贫血和黄疸患者,被诊断为三杂合子β-thal[IVS-II-654(C>T)突变,HbZürich-Langstrasse(HBB:c.151A>T)突变和HbG-Siriraj(HBB:c.22G>A)突变]通过基因测序。然而,他的电泳图谱是不寻常的:90.8%HbG-Siriraj,5.9%HbA2,3.3%HbF,没有HbA,没有HbZurich-Langstrasse。他的母亲具有β-thal特征(βA/βIVS-II-654),患有轻度贫血,具有经典的电泳图谱(95.1%HbA,4.4%HbA2,0.5%HbF)。他的父亲是HbG-Siriraj(βA/βG-Siriraj)的杂合子,但无症状,具有相应的电泳图谱(63.9%HbA,3.5%HbA2,32.6%HbG-Siriraj)。鉴于家庭研究结果,先证者中的HbZürich-Langstrasse突变被认为是他从母亲那里遗传的βIVS-II-654等位基因上发生的从头突变,产生βIVS-II-654/HbZürich-Langstrasse基因型,这应该被解释为一个新的β0突变。这份报告表明,顺式突变可以混淆基因型-表型相关性,因此,就像DNA测试和血红蛋白分析一样,家庭研究对于准确鉴定β-thal突变也是必不可少的。
β-Thalassemia (β-thal) is caused by mutations on the β-globin genes, causing reduced (β+) or absent (β0) synthesis of the β chains of hemoglobin (Hb). In this report, a 28-year-old male patient with anemia and jaundice, was diagnosed with triple-heterozygous β-thal [an IVS-II-654 (C>T) mutation, a Hb Zürich-Langstrasse (HBB: c.151A>T) mutation and a Hb G-Siriraj (HBB: c.22G>A) mutation] by gene sequencing. However, his electrophoresis pattern was unusual: 90.8% Hb G-Siriraj, 5.9% Hb A2, 3.3% Hb F, no Hb A, no Hb Zürich-Langstrasse. His mother carried a β-thal trait (βA/βIVS-II-654) having mild anemia, with a classical electrophoresis pattern (95.1% Hb A, 4.4% Hb A2, 0.5% Hb F). His father was heterozygous for Hb G-Siriraj (βA/βG-Siriraj) but asymptomatic, with a corresponding electrophoresis pattern (63.9% Hb A, 3.5% Hb A2, 32.6% Hb G-Siriraj). In view of the family study results, the Hb Zürich-Langstrasse mutation in the proband was considered a de novo mutation occurring on the βIVS-II-654 allele that he inherited from his mother, resulting in a βIVS-II-654/Hb Zürich-Langstrasse genotype, which should be interpreted as a novel β0 mutation. This report illustrates that mutations in cis can confound genotype-phenotype correlations, therefore, just as DNA testing and Hb analysis, family study is also indispensable to the accurate identification of β-thal mutations.