Contract grant sponsors: Foundation of Auvergne University; French Ministry of Health (DHOS).
Relevance of Different Cellular Models in Determining the Effects of Mutations on SLC16A2/MCT8 Thyroid Hormone Transporter Function and Genotype–Phenotype Correlation
Article first published online: 1 MAY 2013
© 2013 WILEY PERIODICALS, INC.
Volume 34, Issue 7, pages 1018–1025, July 2013
How to Cite
Capri, Y., Friesema, E. C.H., Kersseboom, S., Touraine, R., Monnier, A., Eymard-Pierre, E., Des Portes, V., De Michele, G., Brady, A. F., Boespflug-Tanguy, O., Visser, T. J. and Vaurs-Barriere, C. (2013), Relevance of Different Cellular Models in Determining the Effects of Mutations on SLC16A2/MCT8 Thyroid Hormone Transporter Function and Genotype–Phenotype Correlation. Hum. Mutat., 34: 1018–1025. doi: 10.1002/humu.22331
Communicated by Madhuri Hegde
- Issue published online: 18 JUN 2013
- Article first published online: 1 MAY 2013
- Accepted manuscript online: 8 APR 2013 04:40PM EST
- Manuscript Accepted: 25 MAR 2013
- Manuscript Received: 6 NOV 2012
- Foundation of Auvergne University
- French Ministry of Health (DHOS)
- monocarboxylate transporter 8;
- thyroid hormone
SLC 16A2, the gene for the second member of the solute carrier family 16 (monocarboxylic acid transporter), located on chromosome Xq13.2, encodes a very efficient thyroid hormone transporter: monocarboxylate transporter 8, MCT8. Its loss of function is responsible in males for a continuum of psychomotor retardation ranging from severe (no motor acquisition, no speech) to mild (ability to walk with help and a few words of speech). Triiodothyronine uptake measurement in transfected cells and, more recently, patient fibroblasts, has been described to study the functional consequences of MCT8 mutations. Here, we describe three novel MCT8 mutations, including one missense variation not clearly predicted to be damaging but found in a severely affected patient. Functional studies in fibroblasts and JEG3 cells demonstrate the usefulness of both cellular models in validating the deleterious effects of a new MCT8 mutation if there is still a doubt as to its pathogenicity. Moreover, the screening of fibroblasts from a large number of patient fibroblasts and of transfected mutations has allowed us to demonstrate that JEG3 transfected cells are more relevant than fibroblasts in revealing a genotype–phenotype correlation.