Papillary thyroid cancer in a patient with congenital goitrous hypothyroidism due to a novel deletion in NIS gene

Iodide transport defect (ITD) is a rare cause of congenital hypothyroidism (CH) caused by sodium/iodide symporter (NIS) gene mutations. We report a novel NIS gene deletion in a patient with congenital hypothyroidism, goiter and papillary thyroid cancer . The proband was a 40 years old woman affected by CH treated unevenly with levothyroxine (L-T4) since the first year of age. She presented with a recurrence of multinodular goiter containing two indeterminate nodules and lack of iodide uptake by thyroid, salivary glands and stomach one month after L-T4 withdrawal. A second thyroidectomy was performed and one nodule was a papillary thyroid carcinoma (PTC) at histology. One proband’s brother was also affected by CH and developed a large multinodular goiter. After extracting genomic DNA from peripheral white blood cells and total RNA from thyroid tissue, all 15 exons of NIS gene were amplified and sequenced. No amplification band was obtained from the genomic DNA of the patient from exons 8 to 12 suggesting a large deletion. Direct sequencing of cDNA revealed a homozygous deletion producing a protein lacking of 185 amino acids. The same defect was present in the affected brother. We describe the first case of a patient with papillary thyroid carcinoma associated with dyshormonogenetic goiter due to a deletion of the NIS protein. The lack of a functioning NIS raises the question of how to complete the treatment of infiltrative PTC in this patient.