Congenital Hypothyroidism Caused by a Novel Homozygous Mutation in the Thyroid Peroxidase Gene

UNLABELLED 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 molecule.