Iodide organification defects resulting from cosegregation of mutated and null thyroid peroxidase alleles

This report describes an intriguing combination of the thyroid peroxidase ( TPO) alleles resulting in an iodide organification defect. Sequence analysi s of the patient's TPO gene showed the presence of T-deletion in exon 14 of the TPO gene (T2512del). From the sequencing pattern. this new mutation of the TPO gene was thought to be homozygous. mRNA transfection studies in wh ich mutated mRNA was transfected to CHO-K, cells by electroporation showed that the cells transfected with mutated mRNA expressed smaller TPO molecule s than those of cells transfected with wild-type mRNA and that they had TPO activity. However, the smaller TPO molecules could not translocate onto th e cell surface. To investigate T2512del in the parents, their genomic DNAs were sequenced. Results showed that the mother had T2512del but the father did not. However, when seven polymorphic positions reported earlier were an alyzed, the mother showed two kinds of nucleotides at four positions but th e patient and father showed only one nucleotide at all seven positions. We suspected a deletion of the TPO gene (2p25) in one of two second chromosome s, and analyzed the patient's chromosomes by FISH using TPO cDNA and N-myc genomic DNA as probes. N-myc genomic DNA exhibited two signals and TPO cDNA only one signal, although the G-band showed no morphological abnormalities . T2512-deleted and 2p25-deleted null alleles cosegregated from her parents . resulting in iodide organification defect in the patient, (C) 2001 Elsevi er Science Ireland Ltd. All rights reserved.