Monoallelic thyroid peroxidase gene mutation in a patient with congenital hypothyroidism with total iodide organification defect

Solange Caires Neves, Paola Rossi Mezalira, Vera M. A. Dias, Antonio J. Chagas, Maria Viana, Hector Targovnik, Meyer Knobel, Geraldo Medeiros-Neto, Ileana G. S. Rubio
2010 Arquivos brasileiros de endocrinologia e metabologia  
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
more » ... ed 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.
doi:10.1590/s0004-27302010000800012 pmid:21340161 fatcat:awu7vsfp4jeplotvljpuk234si