Clinical and Molecular Characteristics of SLC16A2 (MCT8) Mutations in Three Families with the Allan–Herndon–Dudley Syndrome

Francesca Novara, Stefan Groeneweg, Elena Freri, Margherita Estienne, Paolo Reho, Sara Matricardi, Sara Matricardi, Barbara Castellotti, W. Edward Visser, Orsetta Zuffardi, Theo J. Visser

Research output: Contribution to journalArticlepeer-review

Abstract

© 2016 WILEY PERIODICALS, INC. Mutations in the thyroid hormone transporter SLC16A2 (MCT8) cause the Allan–Herndon–Dudley Syndrome (AHDS), characterized by severe psychomotor retardation and peripheral thyrotoxicosis. Here, we report three newly identified AHDS patients. Previously documented mutations were identified in probands 1 (p.R271H) and 2 (p.G564R), resulting in a severe clinical phenotype. A novel mutation (p.G564E) was identified in proband 3, affecting the same Gly564 residue, but resulting in a relatively mild clinical phenotype. Functional analysis in transiently transfected COS-1 and JEG-3 cells showed a near-complete inactivation of TH transport for p.G564R, whereas considerable cell-type-dependent residual transport activity was observed for p.G564E. Both mutants showed a strong decrease in protein expression levels, but differentially affected V max and K m values of T3 transport. Our findings illustrate that different mutations affecting the same residue may have a differential impact on SLC16A2 transporter function, which translates into differences in severity of the clinical phenotype.
Original languageEnglish
Pages (from-to)260-264
Number of pages5
JournalHuman Mutation
Volume38
Issue number3
DOIs
Publication statusPublished - Mar 1 2017

Keywords

  • Allan–Herndon–Dudley Syndrome
  • MCT8
  • SLC16A2
  • thyroid hormone transport

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