A novel mutation in the human thyroid peroxidase gene resulting in a totaliodide organification defect

In this study we describe a novel mutation of the thyroid peroxidase (TPO) gene that resulted in a total iodide organification defect. TPO activity an d thyroxine formation in thyroglobulin in the thyroid gland of the patient were below the limits of detection. However, TPO mRNA was detectable at a s imilar size and concentration as compared with normal thyroid tissues when measured by Northern blot analysis. Sequence analysis of the TPO gene showe d the presence of two mutations, a missense mutation in exon 7 and C insert ion in exon 14. These mutations were heterozygous and located in different alleles. The latter mutation has already been reported as one of the mutati ons of the TPO gene resulting in total iodide organification defect. The fo rmer mutation was further analysed by mRNA transfection studies in which mu tated mRNA was transfected to CHO-K1 cells by electroporation. The results of transfection studies showed that the cells transfected with mutated mRNA expressed similar size TPO molecules to those of cells transfected with wi ld-type mRNA but that they lacked TPO activity. The two mutations of the TP O gene resulting in the total iodide organification defect in the patient c osegregated from her parents.