Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003635 (apraxia)
 2,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FOXP2 is a forkhead transcription factor implicated in developmental verbal dyspraxia, a human speech and language disorder. FOXP2 is expressed in complex patterns during brain, lung, heart, and gut development and on into adulthood. Both the protein sequence and brain expression patterns are highly conserved through much of vertebrate evolution. FOXP2 also contains six ultraconserved regions in its introns, consistent with the idea that FOXP2 is tightly regulated. Previous evidence suggested the presence of three transcription start sites for FOXP2, and we sought to characterize them and determine their cell and tissue specificity. We used 5' RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE) and RT-PCR to identify four transcription start sites for human FOXP2, the fourth being in a novel exon. Two of the transcription start sites, including the one in the novel exon, appear to be more cell line specific and lie in an area of remarkably high conservation. We propose that these two transcription start sites may be of great interest in future studies of FOXP2 regulation.
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PMID:Multiple transcription start sites for FOXP2 with varying cellular specificities. 1831 64

Heterozygous mutations in FOXP2, which encodes a forkhead transcription factor, have been shown to cause developmental verbal dyspraxia and language impairment. FOXP2 and its closest homolog, FOXP1, are coexpressed in brain regions that are important for language and cooperatively regulate developmental processes, raising the possibility that FOXP1 may also be involved in developmental conditions that are associated with language impairment. In order to explore this possibility, we searched for mutations in FOXP1 in patients with intellectual disability (ID; mental retardation) and/or autism spectrum disorders (ASD). We first performed array-based genomic hybridization on sporadic nonsyndromic ID (NSID) (n = 30) or ASD (n = 80) cases. We identified a de novo intragenic deletion encompassing exons 4-14 of FOXP1 in a patient with NSID and autistic features. 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. Luciferase reporter assays showed that the p.R525X alteration disrupts the activity of the protein. Formal assessments revealed that both patients with de novo mutations in FOXP1 also show severe language impairment, mood lability with physical aggressiveness, and specific obsessions and compulsions. In conclusion, both FOXP1 and FOXP2 are associated with language impairment, but decrease of the former has a more global impact on brain development than that of the latter.
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PMID:De novo mutations in FOXP1 in cases with intellectual disability, autism, and language impairment. 2095 Jul 88