A Novel Mutation in NKX2-1 Shows Dominant-Negative Effects Only in the Presence of PAX8.

To date, >100 mutations in NKX2-1 have been described. Most NKX2-1 mutations are assumed to result in brain-lung-thyroid syndrome through haploinsufficiency, and only five NKX2-1 mutations with dominant-negative effects have been reported so far. In this case report, an additional patient with brain-lung-thyroid syndrome is reported, carrying a novel heterozygous mutation, c.533G>C (p.R178P), in the homeobox of NKX2-1. This mutation has been proven to be a dominant-negative mutation by an in vitro functional assay. Of note, the dominant-negative effect of R178P-NKX2-1 was shown only in the presence of PAX8.