title: Five novel inactivating mutations in the thyroid peroxidase gene responsible for congenital goiter and iodide organification defect.
abstract: Thyroid peroxidase (TPO) defects, typically transmitted as autosomal recessive traits, result in hypothyroid goiters with failure to convert iodide into organic iodine. We analyzed the TPO gene in 14 unrelated patients with clinical evidence of iodide organification defects. Seven of the affected individuals harbored mutations in the TPO gene; one was compound heterozygous, the others were simply heterozygous for TPO mutations. Five novel mutations have been identified, one of which was found to be a single nucleotide deletion, while the other four were single nucleotide substitutions. A frameshift mutation c.387delC was detected in exon 5 which leads to an early termination signal in exon 7 (p.N129fsX208). Two missense mutations were identified in exon 8. The first, a c.920A>C transversion that results in a p.N307T substitution, was found in two patients. The second, a c.1297G>A transition, results in p.V433M. A c.1496C>T transition was detected in exon 9 that caused the substitution p.P499L. Finally, in exon 14 a c.2422T>C transition was identified, causing a p.C808R change. In addition, the previously reported GGCC duplication in exon 8 (c.1186_1187insGGCC; p.R396fsX472) was also detected in two affected individuals, one of whom was a compound heterozygous (p.R396fsX472/p.V433M).
authors.affiliation: Laboratorio de Biología Molecular, Cátedra de Genética y Biología Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Carina M
authors.initials: CM
authors.lastname: Rivolta
authors.forename: Sebastián A
authors.initials: SA
authors.lastname: Esperante
authors.forename: Laura
authors.initials: L
authors.lastname: Gruñeiro-Papendieck
authors.forename: Ana
authors.initials: A
authors.lastname: Chiesa
authors.forename: Christian M
authors.initials: CM
authors.lastname: Moya
authors.forename: Sabina
authors.initials: S
authors.lastname: Domené
authors.forename: Viviana
authors.initials: V
authors.lastname: Varela
authors.forename: Héctor M
authors.initials: HM
authors.lastname: Targovnik
mesh_terms: D016368:Frameshift Mutation; D020868:Gene Silencing; D005808:Genes, Recessive / Q000235:genetics; D006042:Goiter / Q000151:congenital / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D007037:Hypothyroidism / Q000201:enzymology / Q000235:genetics; D007453:Iodide Peroxidase / Q000235:genetics*; D007454:Iodides / Q000378:metabolism*; D009154:Mutation; D020125:Mutation, Missense; D013961:Thyroid Gland / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*
chemical_list: D007454:Iodides; D007453:Iodide Peroxidase