Antonio J Amor1, Irene Halperin1, Rocίo Alfayate2, Victoria M Borrás3, Arancha Escribano4, Cintia González5, Antonio Gutirrez4, Montserrat Mauri2, Pilar Pérez6, Antonio Picό2, Irene Vourliotaki7, Josep Oriola8. 1. Endocrinology and Nutrition Department, Hospital Clίnic i Universitari, Barcelona, Spain. 2. Endocrinology and Nutrition Department, Hospital General Universitario, Alicante, Spain. 3. Pediatrics Department, Hospital General de Granollers, Barcelona, Spain. 4. Pediatrics Department, Hospital Virgen de la Arrixaca, Murcia, Spain. 5. Endocrinology and Nutrition Department, Hospital Sant Pau, Barcelona, Spain. 6. Pediatrics Department, Hospital Marina Baixa, Alicante; Spain. 7. Endocrinology and Metabolism Department, Venizelio General Hospital, Heraklio, Crete, Greece. 8. Biochemistry and Molecular Genetics Department, Hospital Clίnic i Universitari, Barcelona, Spain.
Abstract
OBJECTIVE: The aim of the study was to describe the clinical, biochemical, and genetic features of a sample of Mediterranean patients with RTH (resistance to thyroid hormone) due to mutations in TRβ (thyroid hormone receptor beta) referred to our institution during the last 15 years. DESIGN: 166 blood samples were received for RTH genetic testing between January 1997 and December 2011. Genetic testing was performed by PCR amplification followed by sequencing of exons 7, 8, 9, and 10. Clinical and biochemical features were obtained from available information sent by referring hospitals. RESULTS: Mutations were identified in 50 patients (29 probands and 21 relatives). 64% were women, and mean ± stdev age at diagnosis among probands was 33.2 ± 20.5 years. The following clinical features were recorded: goiter in 50%, hyperkinetic behavior in 32%, and tachycardia in 29%. Up to 19% of the probands had undergone some type of thyroidal ablative therapy before diagnosis. As for biochemical features, mean ± stdev TSH was 10.2 ± 21.4 mUI/L, and mean ± stdev fT4 was 35.5 ± 10.8 pmol/L. We found four new mutations: p.Phe451Leu, p.Pro452Arg, p.Glu457Gly, and p.Phe459Leu. CONCLUSIONS: The clinical and biochemical characteristics of our samples of Mediterranean populations with RTH were similar to those described in the published literature. Interestingly, in our populations we have identified four novel mutations in the TRβ gene.
OBJECTIVE: The aim of the study was to describe the clinical, biochemical, and genetic features of a sample of Mediterranean patients with RTH (resistance to thyroid hormone) due to mutations in TRβ (thyroid hormone receptor beta) referred to our institution during the last 15 years. DESIGN: 166 blood samples were received for RTH genetic testing between January 1997 and December 2011. Genetic testing was performed by PCR amplification followed by sequencing of exons 7, 8, 9, and 10. Clinical and biochemical features were obtained from available information sent by referring hospitals. RESULTS: Mutations were identified in 50 patients (29 probands and 21 relatives). 64% were women, and mean ± stdev age at diagnosis among probands was 33.2 ± 20.5 years. The following clinical features were recorded: goiter in 50%, hyperkinetic behavior in 32%, and tachycardia in 29%. Up to 19% of the probands had undergone some type of thyroidal ablative therapy before diagnosis. As for biochemical features, mean ± stdev TSH was 10.2 ± 21.4 mUI/L, and mean ± stdev fT4 was 35.5 ± 10.8 pmol/L. We found four new mutations: p.Phe451Leu, p.Pro452Arg, p.Glu457Gly, and p.Phe459Leu. CONCLUSIONS: The clinical and biochemical characteristics of our samples of Mediterranean populations with RTH were similar to those described in the published literature. Interestingly, in our populations we have identified four novel mutations in the TRβ gene.
Authors: Luciano S Ramos; Marina M L Kizys; Ilda S Kunii; Angela M Spinola-Castro; Suzana Nesi-França; Ricardo A Guerra; Cleber P Camacho; João R M Martins; Rui M B Maciel; Magnus R Dias-da-Silva; Maria I Chiamolera Journal: Endocrine Date: 2018-07-19 Impact factor: 3.633