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Relevance of Different Cellular Models in Determining the Effects of Mutations on SLC 16 A 2/ MCT 8 Thyroid Hormone Transporter Function and Genotype–Phenotype Correlation
Author(s) -
Capri Yline,
Friesema Edith C.H.,
Kersseboom Simone,
Touraine Renaud,
Monnier Aurélie,
EymardPierre Eléonore,
Des Portes Vincent,
De Michele Giusseppe,
Brady Angela F.,
BoespflugTanguy Odile,
Visser Theo J.,
VaursBarriere Catherine
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22331
Subject(s) - missense mutation , biology , monocarboxylate transporter , phenotype , solute carrier family , transporter , genotype , transfection , genetics , mutation , hormone , loss function , gene , endocrinology
SLC 16 A 2 , the gene for the second member of the solute carrier family 16 (monocarboxylic acid transporter), located on chromosome X q13.2, encodes a very efficient thyroid hormone transporter: monocarboxylate transporter 8, MCT 8. 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 MCT 8 mutations. Here, we describe three novel MCT 8 mutations, including one missense variation not clearly predicted to be damaging but found in a severely affected patient. Functional studies in fibroblasts and JEG 3 cells demonstrate the usefulness of both cellular models in validating the deleterious effects of a new MCT 8 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 JEG 3 transfected cells are more relevant than fibroblasts in revealing a genotype–phenotype correlation.