Journal of Clinical Endocrinology & Metabolism, Vol 81, 2023-2026, Copyright © 1996 by Endocrine Society

ARTICLES

A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism

N de Roux, M Polak, J Couet, J Leger, P Czernichow, E Milgrom and M Misrahi
INSERM U135 Hormones et Reproduction et laboratoire d'Hormonologie et Biologie Moleculaire, Hopital de Bicetre, Kremlin-Bicetre, France.

Until recently, neonatal hyperthyroidism has been considered to be related to the transplacental passage of thyroid-stimulating Ig present in the serum of the mother. We report here the case of a newborn who presented with severe hyperthyroidism, diffuse goiter, and important ocular signs (eyelid retraction and possibly proptosis). However, the absence of thyroid pathology in the parents and the lack of antithyroid antibodies in the mother and in the patient led us to suspect a nonimmune aetiology. Direct genomic sequencing of the last exon of the TSH receptor in the patient revealed a T-->C transversion yielding to a Met453-->Thr heterozygous substitution in the second transmembrane domain of the receptor. The mutation was absent in both parents. Eukaryotic expression analysis in COS-7 cells yielded a mutated receptor that produced constitutive activation of adenylate cyclase without enhancement of phospholipase C activity.

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