Congenital hypothyroidism caused by a novel homozygous mutation in the thyroid peroxidase gene

Congenital primary hypothyroidism occurs in one out of 4,000 births. About 20% of cases are due to defects in thyroid hormonogenesis. We report on a German girl with congenital hypothyroidism due to a mutation in the thyroid peroxidase (TPO) gene who had elevated serum levels of thyroglobulin during periods of hyperthyrotropinemia. Methods: The TPO gene was sequenced directly from genomic DNA. Results: The patient had a novel homozygous mutation (R314W) in the TPO gene. The unaffected parents were non-consanguineous and both heterozygous carriers of the mutation. Fifty normal individuals did not harbor the mutation ruling out a common polymorphism. Conclusion: The identified TPO gene mutation (R314W) is very likely the genetic cause for hypothyroidism in the reported child. R314W has not been described before and codes for a presumably inactive TPO molecules.