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.
Int J Lab Hematol
; 45(1): 90-95, 2023 Feb.
Article
in En
| MEDLINE
| ID: mdl-36054783
ABSTRACT
INTRODUCTION:
Though an increase in Hb A2 is one of the most key markers of ß-thal carriers, a few independent cases are reported to show elevated Hb A2 levels caused by mutations in other genes beyond ß-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 ß-thalassemic or KLF1 mutations.RESULTS:
Of these 1439 individuals with elevated Hb A2 , 1381 had a molecular defect in globin genes, and most were ß-thalassemic mutation; 10 had a molecular defect in KLF1 gene. Finally, among the 38 individuals without ß-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 ß-thal mutation and a SUPT5H variant might present moderate ß-thaelassemia, these findings emphasized the importance of comprehensive molecular diagnosis to prevent birth defects of ß-thaelassemia caused by rare mutations from modifier genes.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hemoglobin A2
/
Beta-Thalassemia
Type of study:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Limits:
Humans
Language:
En
Journal:
Int J Lab Hematol
Journal subject:
HEMATOLOGIA
Year:
2023
Document type:
Article