In mouse, stronger effects were related to earlier exposure or specific genetic background such as either Pax8 or Nkx2-1 haploinsufficiency, both associated to hypothyroidism in humans.
This condition has been reported in mice with hypothyroidism associated with induced deficiency in paired box 8 and NK2 homeobox 1, sonic hedgehog, or T-box 1.
Haplo-insufficiency of TTF-1 in humans causes hypothyroidism, respiratory dysfunction and recurring pulmonary infections, underlining the importance of optimal TTF-1 levels for the maintenance of thyroid and lung function.
To determine whether the hypothyroidism is of central or primary origin, we examined the bioactivity of TSH, thyroidal response to exogenous TSH and the expression of genes regulated by TTF1.
Therefore, the unfavorable outcome in patients with CH, especially those with choreoathetosis and pulmonary symptoms, can be explained by mutations in the NKX2-1 gene rather than by hypothyroidism.