Two Novel Mutations in the Thyroid Hormone Receptor β in Patients with Resistance to Thyroid Hormone (RTH β): Clinical, Biochemical, and Molecular Data.
The syndrome of resistance to thyroid hormone (RTH β) is an inherited disorder characterized by variable tissue hyposensitivity to 3,5,30-L-triiodothyronine (T(3)), with persistent elevation of free-circulating T(3) (FT(3)) and free thyroxine (FT(4)) 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.
Department of Pediatrics, Faculty of Medical Sciences (FCM), University of Campinas (UNICAMP), Campinas, Brazil.|Center of Molecular Biology and Genetic Engineering (CBMEG), UNICAMP, Campinas, Brazil.|Center for Investigation in Pediatrics (CIPED), FCM, UNICAMP, Campinas, Brazil.
A M
AM
Esquiaveto-Aun
Division of Endocrinology, Department of Clinical Medicine, FCM, UNICAMP, Campinas, Brazil.
D E
DE
Zantut-Wittmann
Center of Molecular Biology and Genetic Engineering (CBMEG), UNICAMP, Campinas, Brazil.
R J
RJ
Petroli
Division of Endocrinology, Department of Clinical Medicine, FCM, UNICAMP, Campinas, Brazil.
B S L
BSL
Nakano
Department of Pediatrics, Faculty of Medical Sciences (FCM), University of Campinas (UNICAMP), Campinas, Brazil.|Center for Investigation in Pediatrics (CIPED), FCM, UNICAMP, Campinas, Brazil.
G
G
Guerra-Júnior
Department of Pediatrics, Faculty of Medical Sciences (FCM), University of Campinas (UNICAMP), Campinas, Brazil.|Center for Investigation in Pediatrics (CIPED), FCM, UNICAMP, Campinas, Brazil.
S H V
SHV
de Lemos-Marini
Center of Molecular Biology and Genetic Engineering (CBMEG), UNICAMP, Campinas, Brazil.
M P
MP
de Mello
D000293:Adolescent; D002675:Child, Preschool; D005260:Female; D006801:Humans; D009154:Mutation; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*; D018382:Thyroid Hormone Resistance Syndrome / Q000235:genetics*
D037042:Thyroid Hormone Receptors beta