A Novel Mutation in Thyroid Peroxidase Gene Causing Congenital Goitrous Hypothyroidism in a German-Thai Patient.

Thyroid dyshormonogenesis is responsible for 10-15% of all cases of congenital hypothyroidism and is usually inherited. We report a 26-year-old German-Thai male with congenital hypothyroidism caused by a compound heterozygous mutation in the thyroid peroxidase (TPO) gene. He was diagnosed with congenital goitrous hypothyroidism at 4 months of age and had been treated with levothyroxine replacement therapy. His goiter size had increased due to poor compliance to treatment. Ultrasonography of the thyroid gland showed a pattern suspicious for malignancy. The patient later underwent near-total thyroidectomy. Pathologic examination results were consistent with a multinodular goiter and no malignancy. Genetic analyses by direct sequencing of the entire exons and flanking regions of the TPO gene were performed in the index case and family members. The analyses revealed a compound heterozygote of novel TPO mutation of c.1727C>T in exon 10 resulting in amino acid substitution (p.Ala576Val) and c.2268_2269insT in exon 13 causing a frameshift mutation which introduced a stop codon after the insertion site. The latter has been reported in Chinese subjects. However, there is no previous report of c.1727C>T mutation in the literature. We found the allele contained a novel exon 10 mutation inherited from the patient's German mother and an exon 13 mutation from his Thai father. Analysis using two bioinformatic software programs indicated that this variant was likely to cause damage in the resulting protein molecule. The present report emphasizes the importance of regular follow-up and patient compliance to levothyroxine replacement in patients with goitrous congenital hypothyroidism to avoid prolonged stimulation of thyroid tissue by thyroid-stimulating hormone.