Department of Clinical Genetics/LDGA, Leiden University Medical Center, P.O. Box 9600, 2333 ZC Leiden, The Netherlands.
Department of Congenital and Hereditary Diseases, Charles Nicolle Hospital, Tunis 3000, Tunisia.
Int J Mol Sci. 2024 Aug 16;25(16):8928. 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.
众所周知,修饰因子在改善或加剧隐性遗传疾病(如镰状细胞病和地中海贫血)患者和携带者的疾病表型方面发挥着作用。在这里,我们综述了最近描述的携带失活功能变异体与β地中海贫血样表型相关联的文献,包括特征性的 HbA 水平升高。在β地中海贫血携带者中, 作为修饰因子的作用是从三个报道的病例中明显的,其中观察到的 和 基因变异的复合杂合性类似于轻度β地中海贫血中间型表型。收集和回顾不同的 变异体和血液学参数,以提供对血液学表达的可能影响的见解,以及携带者和患者的潜在疾病机制。