Thyroid peroxidase(TPO) deficiency due to biallelic TPO mutation is known as a representative genotype of congenital hypothyroidism (CH). CH is a congenital endocrine disorder that appears in 1/2,000 to 4,000 newborns. In most cases CH is caused by embryogenesis of the thyroid but the minority is caused by errors in thyroid metabolism. TPO mutation is known as a cause of rare genetic defects in thyroid metabolism. We hereby report a new homozygous TPO mutation (9491; ex 11; c. G 1964 T: p. C 655 F) as a result of the genetic screening based on the next generation sequencing. TPO is an enzyme that plays an important role in thyroid hormone production, and around 70 TPO mutations have been announced around the world, but this mutation is different from any known mutations. The male patient, the fourth child of healthy Japanese parents, born at term after an uneventful pregnancy and delivery. His parents are consanguineous married. He did not have thyroid stimulating hormone based new born screening. In Japan, mass screening for congenital hypothyroidism has been in effect since 1979, but his birth was before that. He continued to be somnolent, could not drink breast milk, was hospitalized immediately after birth. Hypothyroidism was revealed by examination at half a year after birth. Thyroid hormone replacement therapy was started from that time and thyroid function was kept normal up to adult. Although he has a mild intelligence decline, with no difficulty in daily life and there was no problem in the growth process including the second growth. This patient has been treated with levothyroxine, and now thyroid hormone levels are within normal range. He has a very mild goiter, and the palpation touches the soft thyroid gland. Also, the size of the thyroid gland has no obvious left-right difference. In vitro functional analysis using CHO cells, whether the novel TPO mutation causes a partial loss of enzyme activity or not is under investigation. This TPO mutations (G1964T:p.C655F) was introduced by site-directed mutagenesis. Stable CHO cell lines expressing each TPO protein (WT, G1964T:p.C655F) were established using the piggyback system according to the manufacturers protocol. On the days announcement we would like to present the data of Western blotting using anti-TPO rabbit monoclonal antibody ab109383 and the results of the assay for quantifying thyroid peroxidase activity using Amplex Red reagent and H2O2.
18 - 21 May 2019
European Society of Endocrinology