Speech/Language Disorders Database

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Gene / phenotype associations for FOXP1

  • Click column headers to sort. Click to expand any row to see more details about the particular assertion of an association between variants of FOXP1 and a particular phenotypic variable.
  • Click the Pubmed IDs in the last column to link out to the primary research article. Click the links in the last column to download the full Genotype-Phenotype record as JSON or XML formatted text.
Entrez Id Symbol Location Disorder Brief Phenotype Reference Year Download
27086 FOXP1 3p14.1 Expressive language impairment Hamdan et al 2010 JSON | XML

Additional Phenotype Details: May be assessed using the expressive language scale of the Clinical Evaluation of Language Fundamentals (CELF-R) battery (Semel et al. 1992).


Semel EM, Wiig EH, Secord W (1992) Clinical evaluation of language fundamentals—revised. Phychological Corporation, San Antonio.

Basic Study Type:  Candidate gene sequencing

Study Cohort: 
"We studied sporadic cases with nonsyndromic ID (NSID), ASD, or both NSID and ASD, most of which were of French Canadian origin. . .The NSID cases were selected with the use of previously described criteria [16]. The sporadic ASD patients were diagnosed according to DSM-IV criteria and were selected on the basis of a positive Autism Diagnostic Interview-Revised (ADI-R) and/or Autism Diagnostic Observation Schedule-Generic (ADOS-G). We used 570 healthy individuals as controls, including 285 French Canadians and 285 European individuals who were evaluated and found not to have cognitive dysfunction, neuropsychiatric symptoms, or family history of neuropsychiatric problems, as detailed elsewhere [17]. Blood samples were collected from all members of these cohorts and from their parents, with informed consent and after approval of the study by institutional ethics committees."

For array-based genomic hybridization:

30 subjects with sporadic nonsyndromic intellectual disability (NSID)
80 subjects autism spectrum disorders (ASD)
Both parents of each case

For sequencing FOXP1 coding exons:

110 NSID, 135 ASD, 570 control

Both patients in whom the authors identified de novo mutations in FOXP1 had NSID. One had autism; the other showed autistic features. "Formal assessments revealed that both patients. . .also show severe language impairment, mood lability with physical aggressiveness, and specific obsessions and compulsions."

Genotyping Methods: 
Genome-Wide Human Affymetrix 5.0 SNP arrays were used to check the effect of copy number change on FOXP1 in 80 subjects with ASD (including 27 with ID) and their parents. The 6.0 version was used for 30 subjects will NSID and their parents.

Multiplex ligation-dependent probe amplification (MLPA) analysis was used to confirm the intragenic FOXP1 deletion in patient A.

"We next sequenced all the coding exons and intron-exon boundaries of the longest FOXP1 isoform (FOXP1a; 16 coding exons) in 110 cases with NSID, 84 cases with ASD, and 51 cases with both NSID and ASD, as well as in 570 controls."

Other Details: 
Diagnostic criteria for NSID:

From Hamdan et al 2009, "Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation," N. Engl. J. Med. 360, 599–605:
"The diagnosis of mental retardation was made on a clinical basis with the use of standardized developmental or IQ tests. All patients were examined by at least one experienced clinical geneticist, who ruled out the presence of specific dysmorphic features. For all patients, the birth weights and history of postnatal growth were within the normal range, and the head circumference was normal at birth. Mental retardation was unexplained in these patients despite standard investigations, including karyotyping, subtelomeric fluorescence in situ hybridization analysis, or comparative genomic hybridization targeting regions associated with known syndromes, molecular testing for the common expansion mutation in FMR1, and computed tomography or magnetic resonance imaging of the brain."

Diagnostic criteria for ASD:

"The sporadic ASD patients were diagnosed according to DSM-IV criteria and were selected on the basis of a positive Autism Diagnostic Interview-Revised (ADI-R) and/or Autism Diagnostic Observation Schedule-Generic (ADOS-G)."

To test the mutation's effect on FOXP1 activity:

"The p.R525X mutation was introduced into the full-length coding sequence of the FOXP1 longest isoform (FOXP1a; obtained from Kazusa DNA Research Institute, Japan) and subcloned into the mammalian expression vector pcDNA4HisMax (Invitrogen). Human embryonic kidney (HEK) 293 cells were then cotransfected with the use of Fugene 6 (Roche) in 24-well plates, with 400 ng of pcDNA4HisMax without an insert or containing either the wild-type (WT) FOXP1 or the FOXP1-R525X cDNA, along with 50 ng of pGL3 promoter construct (Promega) (in which the SV40 promoter drives a firefly luciferase reporter). In order to account for variations in transfection efficiency and variation in cell number, cells were also cotransfected with 50 ng of a Renilla luciferase construct (pRL-TK; Promega) driven by the HSVthymidine kinase promoter, which is not affected by FOXP1. Cells were lysed 48 hr after transfection and quantified for firefly and Renilla luciferase activities with the use of the Dual Luciferase Reporter Assay System (Promega)."


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