Characterization of a recurrent missense mutation in the forkhead DNA-binding domain of FOXP1

Authors

Tyler B. Johnson, Sanford Research
Keegan Mechels, Sanford Research
Ruth Ellen Anderson, Sanford Research
Jacob T. Cain, Sanford Research
David A. Sturdevant, Sanford Research
Stephen Braddock, Saint Louis University School of Medicine
Hailey Pinz, Saint Louis University School of Medicine
Mark A. Wilson, University of Nebraska - LincolnFollow
Megan Landsverk, University of South Dakota
Kyle J. Roux, Sanford ResearchFollow
Jill M. Weimer, Sanford ResearchFollow

ORCID IDs

0000-0002-6431-942X

0000-0003-0230-9979

Date of this Version

2018

Citation

SCIENTIFIC REPORTS | (2018) 8:16161

Comments

(2018) 8:16161

Open access

DOI:10.1038/s41598-018-34437-0

Abstract

Haploinsufficiency of Forkhead box protein P1 (FOXP1), a highly conserved transcription factor, leads to developmental delay, intellectual disability, autism spectrum disorder, speech delay, and dysmorphic features. Most of the reported FOXP1 mutations occur on the C-terminus of the protein and cluster around to the forkhead domain. All reported FOXP1 pathogenic variants result in abnormal cellular localization and loss of transcriptional repression activity of the protein product. Here we present three patients with the same FOXP1 mutation, c.1574G>A (p.R525Q), that results in the characteristic loss of transcription repression activity. This mutation, however, represents the first reported FOXP1 mutation that does not result in cytoplasmic or nuclear aggregation of the protein but maintains normal nuclear localization.