Intellectual disability with language impairment and with or without autistic features is a neurodevelopmental disorder characterized by global developmental delay particularly affecting speech and motor skills, dysmorphic facial features, and sometimes autistic features and/or behavioral problems. This disease is associated with autosomal dominant mutations in FOXP1.
This is one of several diseases associated with the four genes in the P subfamily of the forkhead box transcription factor family (FOXP1, FOXP2, FOXP3, FOXP4). Mutations in FOXP2 are associated with speech-language disorder 1 (MIM:602081), and mutations in FOXP3 with immunodysregulation, polyendocrinopathy, and enteropathy, X-linked (MIM:304790).
The human FOXP1 gene has been introduced into flies (Hsap\FOXP1UAS.Tag:HA), but this allele has not yet been characterized.
There is a single orthologous gene in Drosophila, FoxP, which has also been used to model operant self-learning disorders; see FBhh0000641. FoxP is a member of the Forkhead family of transcription factors, all carrying a ~110 amino acid Forkhead-box (FOX) domain that serves as a DNA-binding domain. Given that there are four human orthologs with distinct phenotypes, mutations in the Drosophila FoxP may not fully model these human disorders, or may model more than one of them. Multiple alleles have been generated for FoxP, including null and hypomorphic alleles, RNAi targeting constructs, a GAL4 insertion line and P-element insertions.
FoxP is expressed in neurons of the larval and adult brain. Null mutants of FoxP are 70% pupal lethal. Adult escapers have shorter lifespans, undersized mushroom body α lobes, disorganized synaptic architecture, and smaller dendritic fields. Behaviorally, they show a reduced ability to walk and fly, and impaired habituation learning. When allowed to move freely, they maintain a shorter distance between themselves and other flies, a social interaction phenotype seen in other Drosophila models of autism spectrum disorder.
[updated May 2019 by FlyBase; FBrf0222196]
[INTELLECTUAL DEVELOPMENTAL DISORDER WITH LANGUAGE IMPAIRMENT AND WITH OR WITHOUT AUTISTIC FEATURES; IDDLA](https://omim.org/entry/613670)
[FORKHEAD BOX P1; FOXP1](https://omim.org/entry/605515)
FOXP1 and FOXP2, in particular among the FOXP genes, have overlapping mutant phenotypes that both share defects in expressive language (Bacon and Rappold 2012, pubmed:22736078).
Mental retardation with language impairment and with or without autistic features is a neurodevelopmental disorder characterized by global developmental delay with moderate to severe speech delay that particularly affects expressive speech. Common dysmorphic features include broad forehead, downslanting palpebral fissures, short nose with broad tip, relative macrocephaly, frontal hair upsweep, and prominent digit pads. Gross motor skills are also delayed. Some patients have autistic features and/or behavioral problems. All reported cases have occurred de novo (review by Le Fevre et al., 2013; pubmed:24214399). [from MIM:613670; 2017.09.29]
Mental retardation with language impairment and with or without autistic features is caused by heterozygous mutation in the FOXP1 gene. [from MIM:613670; 2017.09.29]
The protein encoded by FOXP1 belongs to the P subfamily of the forkhead box transcription factor family. There are multiple transcript isoforms involved in the regulation of many different developmental processes. [Gene Cards, FOXP1; 2017.10.02]
FOXP1 is a transcriptional repressor that plays a critical role in monocyte differentiation and macrophage function (Shi et al., 2008; pubmed:18799727). [from MIM:605515; 2017.09.29]
Many to one (4 human to 1 Drosophila); the human genes are FOXP1, FOXP2, FOXP3, and FOXP4.
Moderate-scoring ortholog of human FOXP1, FOXP2, FOXP3, and FOXP4 (1 Drosophila to 4 human); Dmel\FoxP shares 38-43% identity and 50-54% similarity with the FOXP1, FOXP2, FOXP3 human genes; it is less closely related to FOXP4.
