Mutation analysis of thyroid peroxidase gene in Chinese patients with total iodide organification defect: identification of five novel mutations

Abstract

Total iodide organification defect (TIOD), where the iodide in the thyroid gland cannot be oxidized and/or bound to the protein, is caused by a defect in the thyroid peroxidase (TPO) gene. Single strand conformation polymorphism analysis was used to screen for mutations in the TPO gene from five unrelated TIOD patients in Taiwan, and five novel mutations were detected. Three of these were frameshift mutations: a single T insertion between nucleotide position 2268 and 2269 (c.2268-2269 insT) in exon 13 and two single C deletions at nucleotide positions 843 (c.843 delC) and 2413 (c.2413 delC) in exon 8 and 14 respectively. The other two were single nucleotide substitutions (c.G1477>A and c.G2386>T) located in exons 9 and 13 respectively. While the former would result in amino acid substitution (Gly493Ser) in the highly conserved region of the TPO polypeptide, the latter would result in either amino acid substitution (Asp796Tyr) or alternative splicing. Of those identified TPO mutations, c.2268-2269 insT was most prevalent and was detected as heterozygous in all but one TIOD patients. All five TIOD patients investigated in this study were compound heterozygous. The method presented in this study could be used for carrier assessment and mutation analysis of newly identified TIOD patients.

Genetic analysis of thyroid peroxidase (<i>TPO</i>) gene in patients whose hypothyroidism was found in adulthood in West Bengal, India

“…TPO being a key enzyme for thyroid hormone synthesis, TPO gene defect (especially non-synonymous cSNPs) can potentially lead to severe defects in thyroid hormone production, due to total iodide organification defects (TIOD) or partial iodide organification defects (PIOD). Screening and identification of mutations in the TPO gene of patients with evidence of TIOD and PIOD has been done by several groups in different countries of the world like Argentina [16], Netherlands [12], Japan [27], Brazil [25], Portugal [28], and China [29]. Majority of the studies related to TPO gene defect was centered on congenital hypothyroidism but our study was based on hypothyroidism detected in adulthood as we tried to evaluate the other potential causes of this disease in this population besides autoimmunity and iodine deficiency.…”

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

“…The frequency of this phenomenon is unexpectedly high. It has been found in around 9% to 65% of the reported TIOD or PIOD patients of different geographic origin (9,(14)(15)(16)(17)(18). In our experience, three out of four TIOD Brazilian patients and three out of six PIOD patients, all with TPO mutations, had only one mutant allele (data not shown).…”

Mutations of the thyroid peroxidase gene in Chinese siblings with congenital goitrous hypothyroidism

“…Mutation analysis of the TPO gene in CGH patients has been reported in various ethnic populations (5,9,16). It is interesting to note that the compound TPO mutations were identified in the Chinese mainland, demonstrating the heterogeneous nature of TPO mutations among different ethnic groups.…”

“…Because exon 8 was too large, it was amplified using two pairs of primers. PCR primers and conditions were described elsewhere (5).…”

“…2012;56/9 unknown. To our knowledge, there are few data collected in the Chinese mainland (4)(5)(6)(7). It is estimated that 15% of CH cases occur as a consequence of defects in thyroid hormone biosynthesis, in which human thyroid peroxidase (TPO) plays an essential role (8).…”