Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation.
Monocarboxylate transporter 8 (MCT8) is a thyroid hormone transporter, the gene of which is located on the X chromosome. We tested whether mutations in MCT8 cause severe psychomotor retardation and high serum triiodothyronine (T3) concentrations in five unrelated young boys. The coding sequence of MCT8 was analysed by PCR and direct sequencing of its six exons. In two patients, gene deletions of 2.4 kb and 24 kb were recorded and in three patients missense mutations Ala150Val, Arg171 stop, and Leu397Pro were identified. We suggest that this novel syndrome of X-linked psychomotor retardation is due to a defect in T3 entry into neurons through MCT8, resulting in impaired T3 action and metabolism.
Friesema
Edith C H
EC
Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands.
Grueters
Annette
A
Biebermann
Heike
H
Krude
Heiko
H
von Moers
Arpad
A
Reeser
Maarten
M
Barrett
Timothy G
TG
Mancilla
Edna E
EE
Svensson
Johan
J
Kester
Monique H A
MH
Kuiper
George G J M
GG
Balkassmi
Sahila
S
Uitterlinden
André G
AG
Koehrle
Josef
J
Rodien
Patrice
P
Halestrap
Andrew P
AP
Visser
Theo J
TJ
D002648:Child; D002675:Child, Preschool; D017353:Gene Deletion; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000097:blood / Q000235:genetics*; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D020125:Mutation, Missense; D011596:Psychomotor Disorders / Q000097:blood / Q000235:genetics*; D027981:Symporters; D014284:Triiodothyronine / Q000097:blood / Q000378:metabolism*
D027501:Monocarboxylic Acid Transporters; C090735:SLC16A2 protein, human; D027981:Symporters; D014284:Triiodothyronine