ESPE Abstracts

Background: The ability to concentrate iodide actively is a characteristic feature of the thyroid gland. This function is mediated through the sodium iodine symporter (NIS), a glycoprotein located in thyrocytes’membrane. Iodide transport defect (ITD) by NIS defects can result in hypothyroidism with variable degree of goiter and low to absent radio iodide uptake. Mutations in SLC5A5 gene encoding NIS are reported to be a rare form of dyshormonogenetic congenital hypothyroidism (CH), with autosomal recessive inheritance pattern.

Objective and hypotheses: To explore a patient with CH and phenotype compatible with NIS defect.

Method: Genomic DNA was explored by next generation sequencing (NGS) targeting 18 genes (SLC5A5 included) involved in congenital hypothyroidism.

Result: A boy was referred for high TSH level on neonatal screening. At D10, congenital hypothyroidism with eutopic thyroid gland was confirmed with: TSH > 150 μui/ml; T4L 1.7 pg/ml [7.5–16]; T3L 1.5 pg/ml [2–4.2]; Thyroglobulin high at 600 ng/ml; Ultrasound showed normal-size thyroid gland 1.4 ml [0.4 – 1.42]; Absence of radio-technetium uptake on scintigraphy. Baby’s parents were relatives second degree. Thyroid hormone supplementation was immediately started with rapid normalisation of hormones’ levels. The DNA analysis revealed a homozygous C>G nonsense mutation in exon 13 SLC5A5 gene resulting in a premature stop at position 531 (p.Tyr531Stop). This mutation has been previously described as compound heterozygous mutation but its impact on iodide transport or cell membrane targeting has not been clearly determined relative to the presence of other heterozygous mutation. This homozygous mutation of NIS leading to complete deletion of the 13^th transmembrane and the carboxy-terminus part of the symporter underlines the role of this segment in the iodide trapping.

Conclusion: We report the first patient with CH and severe ITD by homozygous nonsense mutation (p.Tyr531stop) in NIS encoding gene. NGS targeting CH appears as a high performance tool.