Thyroxine-binding globulin deficiency due to a novel SERPINA7 mutation: Clinical characterization, analysis of X-chromosome inactivation pattern and protein structural modeling

We report a new SERPINA7 variant associated with TBG-PD in three siblings. We named this variant TBG-Brasilia. The X-chromosome inactivation pattern may have accounted for the rare phenotypic expression in a female. The hydrophobic nature of the mutant is predicted to create an apolar patch at the surface, which results in protein aggregation and/or misfolding, potentially responsible for thyroid hormone transport defect.