A stepwise haematological screening and whole-exome sequencing reveal multiple mutations from SUPT5H causing an elevation of Hb A 2 from a cohort of 47336 individuals
A stepwise haematological screening and whole-exome sequencing reveal multiple mutations from SUPT5H causing an elevation of Hb A 2 from a cohort of 47336 individuals
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逐步血液学筛查和全外显子组测序揭示了 SUPT5H 的多个突变导致 47336 名个体的 Hb A 2 升高
DOI：
10.1111/ijlh.13959
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发表时间：
2022
影响因子：
3
通讯作者：
Liu Yanhui
中科院分区：
文献类型：
--
作者：
Lou Jiwu;Ye Yuhua;Sun Manna;Zhao Ying;Fu Youqing;Liu Yanhui
简介：虽然HbA 2升高是β塔尔携带者最重要的标志物之一，但也有少数独立病例报告显示HbA 2升高是由β珠蛋白基因以外的其他基因突变引起的。研究方法：我们回顾了47336人的血液学指标，分析表型-基因型相关性，并确定1439人（3.04%）的HbA 2升高阳性。对无β-地中海贫血或KLF 1突变的阳性样本进行珠蛋白和KLF 1基因分析，并进一步进行全外显子组测序，以分析其遗传原因。结果如下：在1439例HbA 2升高的个体中，1381例存在珠蛋白基因的分子缺陷，大多数为β-地中海贫血突变，10例存在KLF 1基因的分子缺陷。最后，在38名没有β-地中海贫血或KLF 1突变的个体中，有7名被鉴定为SUPT 5 H功能缺失突变。结论：本研究提供了一个队列筛查中导致Hb A2升高的SUPT 5 H突变谱。根据先前的观察，具有β-塔尔突变和SUPT 5 H变体的个体可能呈现中度β-thaelassemia，这些发现强调了综合分子诊断对于预防由修饰基因的罕见突变引起的β-thaelassemia的出生缺陷的重要性。
Introduction: Though an increase in Hb A2 is one of the most key markers of β-thal carriers, a few independent cases are reported to show elevated Hb A2 levels caused by mutations in other genes beyond β-globin gene...Methods: We reviewed the haematological indices of 47336 individuals to analyse the phenotype-genotype correlation and identified 1439 individuals (3.04%) positive in the elevation of Hb A2 . Globin and KLF1 genes analysis was performed, and further whole-exome sequencing was carried to dissect the genetic causes of those positive samples without β-thalassemic or KLF1 mutations...Results: Of these 1439 individuals with elevated Hb A2 , 1381 had a molecular defect in globin genes, and most were β-thalassemic mutation; 10 had a molecular defect in KLF1 gene. Finally, among the 38 individuals without β-thalassemic or KLF1 mutations, 7 were identified to carried a loss-of-function mutation in SUPT5H...Conclusion: This study has provided a mutation spectrum of SUPT5H in a cohort screening leading to the elevation of Hb A2 . According to the previous observations that individuals with a combination of β-thal mutation and a SUPT5H variant might present moderate β-thaelassemia, these findings emphasized the importance of comprehensive molecular diagnosis to prevent birth defects of β-thaelassemia caused by rare mutations from modifier genes.