Iodide Transport defect: Identification of a novel mutation in the carboxy-terminus of the sodium/iodide symporter in a patient with congenital. P1-P896

NICOLA, JP.; MARTIN, M.; SIGNORINO, M.; TESTA, G.; SOBRERO, G.; MUÑOZ, L.; MASINI-REPISO, AM.; MIRAS, M.

Paris

Encuentro; 55th Annual ESPE Meeting; 2016

European Society for Paediatric Endocrinology

SUMMARY AND DISCUSSIONWe report the identification of a novel homozygous missense mutation?G561E?in the gene encoding NIS in a pediatric patient with congenital hypothyroidism.Surprisingly, the mutation G561E is the first NIS mutant to be identified in theintracellular carboxyl terminal region of the protein.The study shows the importance of NIS carboxy terminus in its trafficking to theplasma membrane. Bioinformatics analysis of the carboxy terminus revealed thepresence of linear motifs involved in protein targeting to the plasma membrane.We identified a putative di-leucine motif (L562L563) that could interact with clathrin adapter complex AP-1 involved in the basolateral sorting of proteins (3).Although the mechanism by which G561E impairs NIS activity remains unknown,we hypothesized that the negative charge of the Glu residue may interfere therecognition of the putative dileucine sorting motif L562L563 by adaptor proteins, thus affecting NIS basolateral plasma membrane sorting in polarized cells.