Pathogenic variants in TSHB are known to cause severe isolated central congenital hypothyroidism (CH). In this study, we present the clinical, biochemical, and genetic features of the first patient with a mild central CH phenotype. We identified a novel homozygous variant in TSHB: (Chr1: NM_000549.5):c.290A>G p.(Tyr97Cys) in a newborn girl detected by neonatal CH screening, whose central CH was initially overlooked because of misinterpretation of her plasma-free thyroxine (fT4) concentration. This report adds to the phenotypic spectrum of TSHB variants and underlines the importance of using age-specific fT4 reference intervals to diagnose central CH.
Keywords: TSHβ; isolated central congenital hypothyroidism; protein modeling.