title: A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene.
abstract: Thyroid hormones are iodothyronines that control growth and development, as well as brain function and metabolism. Although thyroid hormone deficiency can be caused by defects of hormone synthesis and action, it has not been linked to a defect in cellular hormone transport. In fact, the physiological role of the several classes of membrane transporters remains unknown. We now report, for the first time, mutations in the monocarboxylate transporter 8 (MCT8) gene, located on the X chromosome, that encodes a 613-amino acid protein with 12 predicted transmembrane domains. The propositi of two unrelated families are males with abnormal relative concentrations of three circulating iodothyronines, as well as neurological abnormalities, including global developmental delay, central hypotonia, spastic quadriplegia, dystonic movements, rotary nystagmus, and impaired gaze and hearing. Heterozygous females had a milder thyroid phenotype and no neurological defects. These findings establish the physiological importance of MCT8 as a thyroid hormone transporter.
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Dumitrescu
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Liao
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Best
authors.forename: Knut
authors.initials: K
authors.lastname: Brockmann
authors.forename: Samuel
authors.initials: S
authors.lastname: Refetoff
mesh_terms: D001483:Base Sequence; D001921:Brain / Q000002:abnormalities*; D002648:Child; D002675:Child, Preschool; D003409:Congenital Hypothyroidism; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics*; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000235:genetics*; D009154:Mutation; D020417:Nystagmus, Congenital / Q000235:genetics; D010375:Pedigree; D011782:Quadriplegia / Q000235:genetics; D013960:Thyroid Function Tests
chemical_list: D027501:Monocarboxylic Acid Transporters