Artículo de revista
Novel pathogenic mechanism suggested by ex vivo analysis of MCT8 (SLC16A2) mutations
Fecha
2009Registro en:
Human Mutation, Volumen 30, Issue 1, 2018, Pages 29-38
10597794
10.1002/humu.20808
Autor
Visser, W. Edward
Jansen, Jurgen
Friesema, Edith C.H.
Kester, Monique H.A.
Mancilla, Edna
Lundgren, Johan
Van Der Knaap, Marjo S.
Lunsing, Roelineke J.
Brouwer, Oebele F.
Visser, Theo J.
Institución
Resumen
Monocarboxylate transporter 8 (MCT8; approved symbol SLC16A2) facilitates cellular uptake and efflux of 3,3′,5-triiodothyronine (T3). Mutations in MCT8 are associated with severe psychomotor retardation, high serum T3 and low 3,3′,5′-triiodothyronine (rT3) levels. Here we report three novel MCT8 mutations. Two subjects with the F501del mutation have mild psychomotor retardation with slightly elevated T3 and normal rT3 levels. T3 uptake was mildly affected in F501del fibroblasts and strongly decreased in fibroblasts from other MCT8 patients, while T3 efflux was always strongly reduced. Moreover, type 3 deiodinase activity was highly elevated in F501del fibroblasts, whereas it was reduced in fibroblasts from other MCT8 patients, probably reflecting parallel variation in cellular T3 content. Additionally, T3-responsive genes were markedly upregulated by T3 treatment in F501del fibroblasts but not in fibroblasts with other MCT8 mutations. In conclusion, mutations in MCT8 result in a decrea