Loss-of-Function Variants in SUPT5H as Modifying Factors in Beta-Thalassemia

Journal article : Review

It is well known that modifiers play a role in ameliorating or exacerbating disease phenotypes in patients and carriers of recessively inherited disorders such as sickle cell disease and thalassemia. Here, we give an overview of the literature concerning a recently described association in carriers of SUPT5H Loss-of-Function variants with a beta-thalassemia-like phenotype including the characteristic elevated levels of HbA2. That SUPT5H acts as modifier in beta-thalassemia carriers became evident from three reported cases in whom combined heterozygosity of SUPT5H and HBB gene variants was observed to resemble a mild beta-thalassemia intermedia phenotype. The different SUPT5H variants and hematologic parameters reported are collected and reviewed to provide insight into the possible effects on hematologic expression, as well as potential disease mechanisms in carriers and patients.

Authors: Harteveld, CL; Achour, A; Fairuz Mohd Hasan, NF; Legebeke, J; Arkesteijn, SJG

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: MDPI
• Journal: International Journal of Molecular Sciences
• Volume: 25
• Issue: 16
• Article number: 8928
• Publication date: 2024-08-16
• Acceptance date: 2024-08-12
• DOI: 10.3390/ijms25168928
• EISSN: 1422-0067
• Language: English
• Keywords: hematology; β-thalassemia intermedia; molecular diagnosis; SUPT5H; hemoglobin; beta-thalassemia; modifying factor
• Subtype: Review