1. Characterization of a recurrent missense mutation in the forkhead DNA-binding domain of FOXP1.
- Author
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Johnson TB, Mechels K, Anderson RH, Cain JT, Sturdevant DA, Braddock S, Pinz H, Wilson MA, Landsverk M, Roux KJ, and Weimer JM
- Subjects
- Autism Spectrum Disorder physiopathology, Child, Preschool, DNA-Binding Proteins genetics, Developmental Disabilities physiopathology, Female, Forkhead Transcription Factors chemistry, Gene Expression Regulation genetics, HEK293 Cells, Haploinsufficiency genetics, Humans, Infant, Intellectual Disability physiopathology, Language Development Disorders genetics, Language Development Disorders physiopathology, Male, Mutation, Missense genetics, Phenotype, Protein Conformation, Protein Domains genetics, Repressor Proteins chemistry, Structure-Activity Relationship, Autism Spectrum Disorder genetics, Developmental Disabilities genetics, Forkhead Transcription Factors genetics, Intellectual Disability genetics, Repressor Proteins genetics
- 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.
- Published
- 2018
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