In addition, sequencing of all coding exons of FOXP1 in sporadic NSID (n = 110) or ASD (n = 135) cases, as well as in 570 controls, revealed the presence of a de novo nonsense mutation (c.1573C>T [p.R525X]) in the conserved forkhead DNA-binding domain in a patient with NSID and autism.
However, in the last few years, novel rare disruptions in FOXP1 have been reported in multiple cases of cognitive dysfunction, including intellectual disability and autism spectrum disorder, together with language impairment.
Together, these data provide critical mechanistic insights into the function of FOXP1 in the developing neocortex and may reveal molecular pathways at risk in ASD.
In particular, Foxp1 regulation of gene expression appears to be crucial for normal hippocampal development, CA1 plasticity, and spatial learning.<b>SIGNIFICANCE STATEMENT</b> Loss-of-function mutations in the transcription factor <i>Forkhead Box P1</i> (<i>FOXP1</i>) lead to autism spectrum disorder and intellectual disability.
Identification of a de novo FOXP1 mutation and incidental discovery of inherited genetic variants contributing to a case of autism spectrum disorder and epilepsy.