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

• Published in: International journal of molecular sciences 2024-08, Vol.25 (16), p.8928
• Main Authors: Harteveld, Cornelis L, Achour, Ahlem, Fairuz Mohd Hasan, Nik Fatma, Legebeke, Jelmer, Arkesteijn, Sandra J G, Huurne, Jeanet Ter, Verschuren, Maaike, Bhagwandien-Bisoen, Sharda, Schaap, Rianne, Vijfhuizen, Linda, Idrissi, Hakima El, Babbs, Christian, Higgs, Douglas R, Koopmann, Tamara T, Vrettou, Christina, Traeger-Synodinos, Joanne, Baas, Frank
• Format: Article
• Language: English
• Subjects: beta-Thalassemia - genetics; Blood diseases; Cell cycle; Gene expression; Genotype & phenotype; Hematology; Hemoglobin; Heterozygote; Humans; Loss of Function Mutation; Mutation; Nuclear Proteins - genetics; Phenotype; Proteins; Review; RNA polymerase; Transcription factors; Transcriptional Elongation Factors - genetics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25168928

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 Loss-of-Function variants with a beta-thalassemia-like phenotype including the characteristic elevated levels of HbA . That acts as modifier in beta-thalassemia carriers became evident from three reported cases in whom combined heterozygosity of and gene variants was observed to resemble a mild beta-thalassemia intermedia phenotype. The different 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.