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

Hum Mutat. 2017 Mar;38(3):260-264. doi: 10.1002/humu.23140. Epub 2017 Jan 5.


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 Vmax and Km 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.

Keywords: Allan-Herndon-Dudley Syndrome; MCT8; SLC16A2; thyroid hormone transport.

MeSH terms

  • Biomarkers
  • Child
  • Child, Preschool
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mental Retardation, X-Linked / diagnosis*
  • Mental Retardation, X-Linked / genetics*
  • Mental Retardation, X-Linked / therapy
  • Monocarboxylic Acid Transporters / genetics*
  • Muscle Hypotonia / diagnosis*
  • Muscle Hypotonia / genetics*
  • Muscle Hypotonia / therapy
  • Muscular Atrophy / diagnosis*
  • Muscular Atrophy / genetics*
  • Muscular Atrophy / therapy
  • Mutation*
  • Pedigree
  • Phenotype*
  • Symporters


  • Biomarkers
  • Monocarboxylic Acid Transporters
  • SLC16A2 protein, human
  • Symporters

Supplementary concepts

  • Allan-Herndon-Dudley syndrome