Mutations in thyroid hormone receptor α1 cause premature neurogenesis and progenitor cell depletion in human cortical development.

Mutations in the thyroid hormone receptor α 1 gene () have recently been identified as a cause of intellectual deficit in humans. Patients present with structural abnormalities including microencephaly, reduced cerebellar volume and decreased axonal density. Here, we show that directed differentiation of mutant patient-derived induced pluripotent stem cells to forebrain neural progenitors is markedly reduced, but mutant progenitor cells can generate deep and upper cortical layer neurons and form functional neuronal networks.