title: Mutations in the iodotyrosine deiodinase gene and hypothyroidism.
abstract: DEHAL1 has been identified as the gene encoding iodotyrosine deiodinase in the thyroid, where it controls the reuse of iodide for thyroid hormone synthesis. We screened patients with hypothyroidism who had features suggestive of an iodotyrosine deiodinase defect for mutations in DEHAL1. Two missense mutations and a deletion of three base pairs were identified in four patients from three unrelated families; all the patients had a dramatic reduction of in vitro activity of iodotyrosine deiodinase. Patients had severe goitrous hypothyroidism, which was evident in infancy and childhood. Two patients had cognitive deficits due to late diagnosis and treatment. Thus, mutations in DEHAL1 led to a deficiency in iodotyrosine deiodinase in these patients. Because infants with DEHAL1 defects may have normal thyroid function at birth, they may be missed by neonatal screening programs for congenital hypothyroidism.
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands. j.morenonavarro@erasmusmc.nl
authors.forename: José C
authors.initials: JC
authors.lastname: Moreno
authors.forename: Willem
authors.initials: W
authors.lastname: Klootwijk
authors.forename: Hans
authors.initials: H
authors.lastname: van Toor
authors.forename: Graziella
authors.initials: G
authors.lastname: Pinto
authors.forename: Mariella
authors.initials: M
authors.lastname: D'Alessandro
authors.forename: Aubène
authors.initials: A
authors.lastname: Lèger
authors.forename: David
authors.initials: D
authors.lastname: Goudie
authors.forename: Michel
authors.initials: M
authors.lastname: Polak
authors.forename: Annette
authors.initials: A
authors.lastname: Grüters
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D006042:Goiter / Q000201:enzymology / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D007453:Iodide Peroxidase / Q000172:deficiency / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D007470:Monoiodotyrosine / Q000378:metabolism; D020125:Mutation, Missense; D016366:Open Reading Frames; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion
chemical_list: D007453:Iodide Peroxidase; D007470:Monoiodotyrosine