Silent but Not Harmless: A Synonymous SLC5A5 Gene Variant Leading to Dyshormonogenic Congenital Hypothyroidism

GEYSELS, ROMINA CELESTE

Frontiers in Endocrinology

Frontiers

Lugar: Laussane; Año: 2022

1664-2392

ackground: Congenital iodide transport defect (ITD) is an uncommon cause ofdyshormonogenic congenital hypothyroidism characterized by the absence of activeiodide accumulation in the thyroid gland. ITD is an autosomal recessive disorder causedby loss-of-function variants in the sodium/iodide symporter (NIS)-coding SLC5A5 gene.Objective: We aimed to identify, and if so to functionally characterize, novel ITD-causingSLC5A5 gene variants in a cohort of five unrelated pediatric patients diagnosed withdyshormonogenic congenital hypothyroidism with minimal to absent 99mTc-pertechnetateaccumulation in the thyroid gland.Methods: The coding region of the SLC5A5 gene was sequenced using Sangersequencing. In silico analysis and functional in vitro characterization of a novelsynonymous variant were performed.Results: Sanger sequencing revealed a novel homozygous synonymous SLC5A5 genevariant (c.1326A>C in exon 11). In silico analysis revealed that the c.1326A>C variant ispotentially deleterious fo