Variable clinical phenotypes in a family with homozygous c.1159G>A mutation in the thyroid peroxidase gene.

BACKGROUND Defects in the thyroid peroxidase (TPO) gene have been associated with goitrous congenital hypothyroidism (CH). CASE REPORT In this study, we report 3 siblings possessing a homozygous mutation, c.1159G>A, but exhibiting different clinical phenotypes in a Malaysian-Malay family. The index patient was diagnosed with CH during a routine neonatal screening but the other 2 siblings appeared to be asymptomatic until the ages of 19 and 12.5, respectively, when they started to develop goiter. RESULTS AND CONCLUSION The mutation was predicted to interrupt the correct splicing of pre-mRNA and also lead to structural alterations in the functional sites of the mutant TPO. The current results suggest the association of goiter development with a homozygous c.1159G>A mutation, but the CH in the index patient could be triggered by other genetic and epigenetic factors distinct from the c.1159G>A mutation.