A Novel SLC5A5 Variant Reveals the Crucial Role of Kinesin Light Chain 2 in Thyroid Hormonogenesis

MASINI-REPISO, ANA MARÍA

JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM

ENDOCRINE SOC

Año: 2021 vol. 106 p. 1867 - 1867

0021-972X

ontext: Iodide transport defect (ITD) (Online Mendelian Inheritance in Man No. 274400) is an uncommon cause of dyshormonogenic congenital hypothyroidism due to loss-of-function variants in the SLC5A5 gene, which encodes the sodium/iodide symporter (NIS), causing defcient iodide accumulation in thyroid follicular cells.Objective: This work aims to determine the molecular basis of a patient?s ITD clinical phenotype.Methods: The propositus was diagnosed with dyshormonogenic congenitalhypothyroidism with minimal 99mTc-pertechnetate accumulation in a eutopic thyroid gland. The propositus SLC5A5 gene was sequenced. Functional in vitro characterization of the novel NIS variant was performed.Results: Sanger sequencing revealed a novel homozygous missense p.G561E NIS variant. Mechanistically, the G561E substitution reduces iodide uptake, because targeting of G561E NIS to the plasma membrane is reduced. Biochemical analyses revealed that G561E impairs the recognition of an adjacent tryptophan-a