Characterization of a Recurrent Missense Mutation in the Forkhead DNA-binding Domain of FOXP1

Overview

Journal Sci Rep

Specialty Science

Date 2018 Nov 3

PMID 30385778

Citations 5

Authors

Tyler B Johnson

Keegan Mechels

Ruthellen H Anderson

Jacob T Cain

David A Sturdevant

Stephen Braddock

Hailey Pinz

Mark A Wilson

Megan Landsverk

Kyle J Roux

Jill M Weimer

Affiliations

Soon will be listed here.

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.

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