A stepwise haematological screening and whole‐exome sequencing reveal multiple mutations from SUPT5H causing an elevation of Hb A2 from a cohort of 47336 individuals. (24th August 2022)

• Record Type: Journal Article
• Authors: Lou, Jiwu; Ye, Yuhua; Sun, Manna; Zhao, Ying; Fu, Youqing; Liu, Yanhui
• Is Part Of: International journal of laboratory hematology. Volume 45:Number 1(2023)
• Page Start: 90
• Page End: 95
• Publication Date: 2022-08-24
• Subjects: haemoglobin A2 -- mutation -- SUPT5H -- thalassemia; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; Hematology -- Periodicals; 616.15005
• DOI: 10.1111/ijlh.13959
• Languages: English
• ISSNs: 1751-5521

Abstract

Abstract: 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.