title: Monoallelic thyroid peroxidase gene mutation in a patient with congenital hypothyroidism with total iodide organification defect.
abstract: The aim of this study was to identify the genetic defect of a patient with dyshormonogenetic congenital hypothyroidisms (CH) with total iodide organification defect (TIOD). A male child diagnosed with CH during neonatal screening. Laboratory tests confirmed the permanent and severe CH with TIOD (99% perchlorate release). The coding sequence of TPO, DUOX2, and DUOXA2 genes and 2957 base pairs (bp) of the TPO promoter were sequenced. Molecular analysis of patient's DNA identified the heterozygous duplication GGCC (c.1186_1187insGGCC) in exon 8 of the TPO gene. No additional mutation was detected either in the TPO gene, TPO promoter, DUOX2 or DUOXA2 genes. We have described a patient with a clear TIOD causing severe goitrous CH due to a monoallelic TPO mutation. A plausible explanation for the association between an autosomal recessive disorder with a single TPO-mutated allele is the presence of monoallelic TPO expression.
authors.affiliation: Thyroid Unit, Cellular and Molecular Endocrinology Laboratory, Faculdade de Medicina da Universidade de São Paulo, SP, Brazil.
authors.forename: Solange Caires
authors.initials: SC
authors.lastname: Neves
authors.forename: Paola Rossi
authors.initials: PR
authors.lastname: Mezalira
authors.forename: Vera M A
authors.initials: VM
authors.lastname: Dias
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Chagas
authors.forename: Maria
authors.initials: M
authors.lastname: Viana
authors.forename: Hector
authors.initials: H
authors.lastname: Targovnik
authors.forename: Meyer
authors.initials: M
authors.lastname: Knobel
authors.forename: Geraldo
authors.initials: G
authors.lastname: Medeiros-Neto
authors.forename: Ileana G S
authors.initials: IG
authors.lastname: Rubio
mesh_terms: D000483:Alleles; D001324:Autoantigens / Q000235:genetics*; D003409:Congenital Hypothyroidism / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007453:Iodide Peroxidase / Q000235:genetics*; D033862:Iron-Binding Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D001324:Autoantigens; D033862:Iron-Binding Proteins; C056658:TPO protein, human; D007453:Iodide Peroxidase