title: Psychomotor retardation caused by a defective thyroid hormone transporter: report of two families with different MCT8 mutations.
abstract: OBJECTIVE
  Monocarboxylate transporter 8 (MCT8) is essential for thyroid hormone (TH) transport in the brain. Mutations in MCT8 are associated with the Allan-Herndon-Dudley syndrome (AHDS), characterized by severe psychomotor retardation and altered serum thyroid parameters. Here we report two novel mutations in MCT8 and discuss the clinical findings.
  
  
  RESULTS
  We describe 4 males with AHDS from two unrelated families varying in age from 1.5 to 11 years. All 4 patients presented with typical clinical signs of AHDS, including severe psychomotor retardation, axial hypotonia, lack of speech, diminished muscle mass, increased muscle tone, hyperreflexia, myopathic facies, high T3, low T4 and rT3, and normal/mildly elevated TSH levels. Comparison of patients at different ages suggests the progressive nature of AHDS. Genetic analyses identified a novel missense MCT8 mutation (p.G495A) in family 1 and a 2.8-kb deletion comprising exons 3 and 4 in family 2. Functional analysis of p.G495A revealed impaired TH transport varying from 20 to 85% depending on the cell context.
  
  
  CONCLUSIONS
  Here we report 4 AHDS patients in unrelated Turkish families harboring novel MCT8 mutations. Despite the widely different mutations, the clinical phenotypes are very similar and findings support the progressive nature of AHDS.
authors.affiliation: Department of Pediatric Endocrinology, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Anık
authors.forename: Simone
authors.initials: S
authors.lastname: Kersseboom
authors.forename: Korcan
authors.initials: K
authors.lastname: Demir
authors.forename: Gönül
authors.initials: G
authors.lastname: Catlı
authors.forename: Uluç
authors.initials: U
authors.lastname: Yiş
authors.forename: Ece
authors.initials: E
authors.lastname: Böber
authors.forename: Alies
authors.initials: A
authors.lastname: van Mullem
authors.forename: Ramona E A
authors.initials: RE
authors.lastname: van Herebeek
authors.forename: Semra
authors.initials: S
authors.lastname: Hız
authors.forename: Ayhan
authors.initials: A
authors.lastname: Abacı
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
mesh_terms: D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000209:etiology / Q000235:genetics; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D027501:Monocarboxylic Acid Transporters / Q000235:genetics* / Q000378:metabolism; D009123:Muscle Hypotonia / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D009133:Muscular Atrophy / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D009154:Mutation / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D027981:Symporters; D013963:Thyroid Hormones / Q000097:blood
chemical_list: D027501:Monocarboxylic Acid Transporters; C090735:SLC16A2 protein, human; D027981:Symporters; D013963:Thyroid Hormones