title: Relevance of different cellular models in determining the effects of mutations on SLC16A2/MCT8 thyroid hormone transporter function and genotype-phenotype correlation.
abstract: 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.
authors.affiliation: INSERM/UMR 1103, CNRS 6293, GReD, Medical school, Clermont-Ferrand, France.
authors.forename: Yline
authors.initials: Y
authors.lastname: Capri
authors.forename: Edith C H
authors.initials: EC
authors.lastname: Friesema
authors.forename: Simone
authors.initials: S
authors.lastname: Kersseboom
authors.forename: Renaud
authors.initials: R
authors.lastname: Touraine
authors.forename: Aurélie
authors.initials: A
authors.lastname: Monnier
authors.forename: Eléonore
authors.initials: E
authors.lastname: Eymard-Pierre
authors.forename: Vincent
authors.initials: V
authors.lastname: Des Portes
authors.forename: Giusseppe
authors.initials: G
authors.lastname: De Michele
authors.forename: Angela F
authors.initials: AF
authors.lastname: Brady
authors.forename: Odile
authors.initials: O
authors.lastname: Boespflug-Tanguy
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.forename: Catherine
authors.initials: C
authors.lastname: Vaurs-Barriere
mesh_terms: D000293:Adolescent; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005347:Fibroblasts / Q000378:metabolism; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011596:Psychomotor Disorders / Q000235:genetics* / Q000503:physiopathology*; D012720:Severity of Illness Index; D027981:Symporters; D013963:Thyroid Hormones / Q000378:metabolism
chemical_list: D027501:Monocarboxylic Acid Transporters; C090735:SLC16A2 protein, human; D027981:Symporters; D013963:Thyroid Hormones