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

GEYSELS, ROMINA CELESTE; BERNAL BARQUERO, CARLOS EDUARDO; MARTÍN, MARIANO; PEYRET, VICTORIA; NOCENT, MARTINA; SOBRERO, GABRIELA; MUÑOZ, LILIANA; SIGNORINO, MALVINA; TESTA, GRACIELA; CASTRO, RICARDO BELISARIO; MASINI-REPISO, ANA MARÍA; MIRAS, MIRTA BEATRIZ; NICOLA, JUAN PABLO

Frontiers in Endocrinology

Frontiers Media S.A.

Año: 2022 vol. 13

ackground: Congenital iodide transport defect (ITD) is an uncommon cause of dyshormonogenic congenital hypothyroidism characterized by the absence of active iodide accumulation in the thyroid gland. ITD is an autosomal recessive disorder caused by 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-causing SLC5A5 gene variants in a cohort of five unrelated pediatric patients diagnosed with dyshormonogenic congenital hypothyroidism with minimal to absent 99mTc-pertechnetate accumulation in the thyroid gland. Methods: The coding region of the SLC5A5 gene was sequenced using Sanger sequencing. In silico analysis and functional in vitro characterization of a novel synonymous variant were performed. Results: Sanger sequencing revealed a novel homozygous synonymous SLC5A5 gene variant (c.1326A>C in exon 11). In silico analysis revealed that the c.1326A>C variant is potentially d