Identification of four novel mutations in the thyroid hormone receptor-β gene in 164 Spanish and 2 Greek patients with resistance to thyroid hormone.
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.


METHODS
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.
Endocrinology and Nutrition Department, Hospital Clίnic i Universitari, Barcelona, Spain.
Antonio J
AJ
Amor
Endocrinology and Nutrition Department, Hospital Clίnic i Universitari, Barcelona, Spain.
Irene
I
Halperin
Endocrinology and Nutrition Department, Hospital General Universitario, Alicante, Spain.
Rocίo
R
Alfayate
Pediatrics Department, Hospital General de Granollers, Barcelona, Spain.
Victoria M
VM
Borrás
Pediatrics Department, Hospital Virgen de la Arrixaca, Murcia, Spain.
Arancha
A
Escribano
Endocrinology and Nutrition Department, Hospital Sant Pau, Barcelona, Spain.
Cintia
C
González
Pediatrics Department, Hospital Virgen de la Arrixaca, Murcia, Spain.
Antonio
A
Gutirrez
Endocrinology and Nutrition Department, Hospital General Universitario, Alicante, Spain.
Montserrat
M
Mauri
Pediatrics Department, Hospital Marina Baixa, Alicante; Spain.
Pilar
P
Pérez
Endocrinology and Nutrition Department, Hospital General Universitario, Alicante, Spain.
Antonio
A
Picό
Endocrinology and Metabolism Department, Venizelio General Hospital, Heraklio, Crete, Greece.
Irene
I
Vourliotaki
Biochemistry and Molecular Genetics Department, Hospital Clίnic i Universitari, Barcelona, Spain.
Josep
J
Oriola
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006042:Goiter / Q000235:genetics; D006115:Greece; D006801:Humans; D006948:Hyperkinesis / Q000235:genetics; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013030:Spain; D013610:Tachycardia / Q000235:genetics; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*; D018382:Thyroid Hormone Resistance Syndrome / Q000235:genetics*; D055815:Young Adult
D037042:Thyroid Hormone Receptors beta