Iwahashi-Odano M, Nagasaki K, Fukami M, et al. - Given that PAX8 is a transcription factor needed for thyroid development, and its mutation causes congenital hypothyroidism (CH), researchers reported the identification and functional characterization of three novel truncating PAX8 mutations located outside the paired domain. Three CH probands had thyroid hypoplasia, diagnosed in the newborn screening frame, and were treated with levothyroxine. Next-generation sequencing-based mutation screening was conducted. According to findings, each proband had novel truncating PAX8 mutations which were I160Sfs*52, Q213Efs*27, and F342Rfs*85. Western blotting exhibited destabilization of the I160fs-PAX8 protein. Clinical and molecular findings of three novel truncating PAX8 mutations located outside the paired domain have been documented. Experiments using cultured cells and recombinant proteins have shown that the C-terminal portion (ie, 363–400 aa) of PAX8 is needed for the PAX8-NKX2-1 interaction.