Two Novel SUPT5H Variants Causing β-Thalassemia Trait Phenotypes.

β-Thalassemia is a common genetic hematological disorder resulting from absent or reduced expression of the β-globin gene (HBB). Beyond defects in HBB itself, defects in genes involving its regulation, such as KLF1, ERCC2, and SUPT5H can cause β-thalassemia-like phenotypes. Here, we identified two novel variants in the SUPT5H gene in two families. Family 1 carried a splice-site variant (c.967-1G > A), while family 2 harbored a frameshift variant (c.2605delC, p.Q869Rfs*85). The hematological profiles of all carriers of SUPT5H variants are consistent with previously reported heterozygous SUPT5H-related traits, underscoring the role of SUPT5H haploinsufficiency in modulating HBB regulation.