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

Area of Science:

• Genetics
• Hematology
• Molecular Biology

Background:

• Genetic modifiers influence disease severity in inherited blood disorders like sickle cell disease and thalassemia.
• Recessive disorders often exhibit variable phenotypes due to genetic and environmental factors.

Purpose of the Study:

• To review the literature on the association between SUPT5H loss-of-function variants and a beta-thalassemia-like phenotype.
• To investigate the role of SUPT5H as a modifier gene in beta-thalassemia carriers.

Main Methods:

• Literature review of reported cases involving SUPT5H and HBB gene variants.
• Analysis of hematologic parameters in individuals with combined heterozygosity.
• Collection and review of different SUPT5H variants.

Main Results:

• A beta-thalassemia-like phenotype, including elevated HbA2 levels, was observed in carriers of SUPT5H loss-of-function variants.
• Three cases demonstrated a mild beta-thalassemia intermedia phenotype in individuals with combined heterozygosity for SUPT5H and HBB variants.

Conclusions:

• SUPT5H loss-of-function variants can act as genetic modifiers in beta-thalassemia.
• Understanding SUPT5H's role provides insight into hematologic expression and disease mechanisms in beta-thalassemia carriers and patients.