An intramolecular ionic interaction linking defective sodium/iodide symporter transport to the plasma membrane and dyshormonogenic congenital hypothyroidism

BERNAL BARQUERO, CARLOS EDUARDO; MARTÍN, MARIANO; GEYSELS, ROMINA CELESTE; PEYRET, VICTORIA; PAPENDIECK, PATRICIA; MASINI-REPISO, ANA MARÍA; CHIESA, ANA ELENA ; NICOLA, JUAN PABLO

THYROID

MARY ANN LIEBERT INC

Lugar: New York; Año: 2021

1050-7256

ackground: The sodium/iodide symporter (NIS) mediates active iodide accumulation in the thyroid follicular cell. Autosomal recessive iodide transport defect (ITD)-causing loss-of-function NIS variants lead to dyshormonogenic congenital hypothyroidism due to deficient iodide accumulation for thyroid hormonogenesis. Here, we aimed to identify, and if so to functionally characterize, novel ITD-causing NIS pathogenic variants in a patient diagnosed with severe dyshormonogenic congenital hypothyroidism due to a defect in iodide accumulation in the thyroid follicular cell, as suggested by non-detectable radioiodide accumulation in a normally located thyroid gland, as well as in salivary glands.Methods: The proposita NIS-coding SLC5A5 gene was sequenced using Sanger sequencing. In silico analysis and functional in vitro characterization of the novel NIS variants was performed.Results: Sanger sequencing revealed novel compound heterozygous SLC5A5 gene variants (c.970-3C>A and c.1106A>T, p.D36