• 作者：Joaquin Lado Abeal^a ; ^b ; ^{joaquin.lado@ttuhsc.edu} ; Ramó ; n Albero Gamboa^c ; David Araujo Vilar^a ; ^d ; Olga Barca Mallo^a ; Ignacio Bernabeú ; Moron^d ; Marí ; a Teresa Calvo^e ; Isabel Castro Piedras^a ; ^b ; Jesú ; s Martin Calamata^f ; Fernando Palos Paz^a ; Roberto Peinó ; ^d ; Diego Peteiro^a ; ^d ; Berta Victoria^a
• 关键词：Sí ; ndrome de resistencia a la acció ; n de las hormonas tiroideas ; Receptor beta de las hormonas tiroideas ; Gen THRB ; Mutació ; n
• 刊名：Medicina Cl铆nica
• 出版年：2011
• 期刊代码：pca254_00257753
• 类别：med
• 出版时间：12 November 2011
• 卷：137
• 期：12
• 页码：551-554
• 文件大小：282 K

Background and objective

Resistance to thyroid hormone (RTH) is a syndrome mostly caused by mutations in thyroid hormone receptor beta gen (THRB). We present five families with RTH phenotype.

Patients and methods

THRB gene sequencing. In vitro studies to evaluate the mutants response to thyroid hormones and their dominant negative effect. Mechanism of resistance in patients with RTH without THRB mutations quantifying expression of regulator of calcineurin 2 (ZAKI4) and Kruppel-like factor 9 (BTEB) genes in patients fibroblast cultures.

Results

THRB mutations were found in three cases: R243Q, R320C, R429Q. Mutants showed a decreased response to T3. R243Q and R320C had a strong dominant negative effect. One subject without THRB mutation showed changes in ZAKI4 and BTEB expression similar to R320C and the other showed expression levels higher than normal controls.

Conclusions

Three cases of RTH were caused by THRB heterozygous mutations but in two cases mutations were not found. THRB mutation carriers and one of the patients without mutations share a similar mechanism of resistance and in the other subject RTH is TR尾 independent.