Horm Metab Res 2015; 47(12): 889-894
DOI: 10.1055/s-0035-1545305
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Two Novel Mutations in the Thyroid Hormone Receptor β in Patients with Resistance to Thyroid Hormone (RTH β): Clinical, Biochemical, and Molecular Data

A. M. Esquiaveto-Aun
1  Department of Pediatrics, Faculty of Medical Sciences (FCM), University of Campinas (UNICAMP), Campinas, Brazil
2  Center of Molecular Biology and Genetic Engineering (CBMEG), UNICAMP, Campinas, Brazil
3  Center for Investigation in Pediatrics (CIPED), FCM, UNICAMP, Campinas, Brazil
,
D. E. Zantut-Wittmann
4  Division of Endocrinology, Department of Clinical Medicine, FCM, UNICAMP, Campinas, Brazil
,
R. J. Petroli
2  Center of Molecular Biology and Genetic Engineering (CBMEG), UNICAMP, Campinas, Brazil
,
B.S. L. Nakano
4  Division of Endocrinology, Department of Clinical Medicine, FCM, UNICAMP, Campinas, Brazil
,
G. Guerra-Júnior
1  Department of Pediatrics, Faculty of Medical Sciences (FCM), University of Campinas (UNICAMP), Campinas, Brazil
3  Center for Investigation in Pediatrics (CIPED), FCM, UNICAMP, Campinas, Brazil
,
S.H. V. de Lemos-Marini
1  Department of Pediatrics, Faculty of Medical Sciences (FCM), University of Campinas (UNICAMP), Campinas, Brazil
3  Center for Investigation in Pediatrics (CIPED), FCM, UNICAMP, Campinas, Brazil
,
M. P. de Mello
2  Center of Molecular Biology and Genetic Engineering (CBMEG), UNICAMP, Campinas, Brazil
› Author Affiliations
Further Information

Publication History

received 22 October 2014

accepted 29 January 2015

Publication Date:
04 March 2015 (online)

Abstract

The syndrome of resistance to thyroid hormone (RTH β) is an inherited disorder characterized by variable tissue hyposensitivity to 3,5,30-l-triiodothyronine (T3), with persistent elevation of free-circulating T3 (FT3) and free thyroxine (FT4) levels in association with nonsuppressed serum thyrotropin (TSH). Clinical presentation is variable and the molecular analysis of THRB gene provides a short cut diagnosis. Here, we describe 2 cases in which RTH β was suspected on the basis of laboratory findings. The diagnosis was confirmed by direct THRB sequencing that revealed 2 novel mutations: the heterozygous p.Ala317Ser in subject 1 and the heterozygous p.Arg438Pro in subject 2. Both mutations were shown to be deleterious by SIFT, PolyPhen, and Align GV-GD predictive methods.