Autism Spectrum Disorders via the FOXP1 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
3763 FOXP1$970.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

Currently, the contribution of de novo and inherited factors to Autism Spectrum Disorders (ASD) risk is estimated to be approximately 50-60% (Krumm et al. 2015) and 25-50% for intellectual disability (ID), with the percentage increasing proportionately with phenotypic severity (McLaren and Bryson 1987). FOXP1 is classified in the Simons Foundation Autism Research Initiative (SFARI) Database as a ‘strong candidate’ gene regarding ASD risk ( However, more than 700 genes total have been associated with ASD features (Bourgeron 2016). One comprehensive study investigating shared clinical features of individuals with FOXP1 putative causative variants from multiple studies described 10 individuals (Le Fevre et al. 2013), however the SFARI gene database indicates there have been as many as 24 reports of affected individuals, half of which were also diagnosed with ASD (

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 FOXP1$690.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity

Overall, de novo copy number variants (CNVs) are estimated to account for approximately 6% of ASD risk (Lim et al. 2013). The contribution of FOXP1 CNVs specifically is unclear; however, 3p interstitial deletions that encompass either solely FOXP1 or additional genes within this region have been reported by multiple sources (Le Fevre et al. 2013; Palumbo et al. 2013; Horn et al. 2010; Carr et al. 2010; Pariani et al. 2009). Individuals with large deletions affecting FOXP1 and additional genes share broad forehead, short, broad nose, and macrocephaly phenotypes with those having deletions affecting FOXP1 exclusively, suggesting these features may be specific to FOXP1 disruption (Le Fevre et al. 2013).

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Clinical Features

Autism Spectrum Disorders (ASD) encompass several neurodevelopmental disorders characterized by varying degrees of social impairment, communication ability, and propensity for restricted interests and repetitive behavior(s) which usually present by age 3. Diagnosis is based on the degree and severity of symptoms and behaviors (Diagnostic and Statistical Manual of Mental Disorders (DSM-5); Levy et al. 2009; McPartland et al. 2016). Comorbidities occur in more than 70% of cases and include intellectual disability (ID), epilepsy, language deficits, and gastrointestinal problems (Sztainberg and Zoghbi 2016). ID specifically refers to significant impairment of cognitive and adaptive development (intelligence quotient, IQ<70) due to abnormalities of brain structure and/or function (American Association of Intellectual and Developmental Disabilities, AAIDD). ID is not a single entity, but rather a general symptom of neurologic dysfunction that is diagnosed before age 18 in ~1-3% of the population (Kaufman et al. 2010; Vissers et al. 2016).

The FOXP1 gene has been implicated in sporadic ASD and ID cases and is associated with global developmental delay with moderate to severe language impairment. Specifically, expressive speech impairment and consonant expression is a hallmark trait of individuals with FOXP1-associated ASD and ID (Le Fevre et al. 2013). Facial features include broad forehead, down-slanting or narrow palpebral fissures, short nose with a broad tip, macrocephaly (variable), frontal upsweep of hair, and prominent fingertip pads. Less common features include widely spaced eyes, ptosis of eyelids, smooth philtrum, sparse lateral eyebrows, and epicanthus (Lozano et al. 2015; Le Fevre et al. 2013; Hamdan et al. 2010).


FOXP1 is a member of the human FOX gene family defined by a DNA binding forkhead box (FOX) domain and involvement in immunological, hematological, and embryological development. FOXP1 is enriched within the brain, including the neocortex, hippocampus, and striatum (Ferland et al. 2003; Teramitsu et al. 2004) and is expressed ubiquitously throughout the central nervous system (Teramitsu et al. 2004). Mouse studies have shown a potential role of FOXP1 in control of motor neuron migration and axon trajectory choice (Palmesino et al. 2010). Members of the FOXP subfamily bind DNA as a homo- or heterodimer. For example, FOXP1 has been shown to work cooperatively in mice with FOXP2, which is also implicated in ASD and ID phenotypes (Le Fevre et al. 2013; Shu et al. 2007). Numerous isoforms of FOXP1 have been described, with the most inclusive transcript encompassing 21 exons, of which exons 6-21 are protein coding (Brown et al. 2008).

FOXP1 pathogenic variants are almost exclusively de novo and include whole and partial gene deletions, translocations, missense, nonsense, and frameshift variants. FOXP1-associated ASD and ID features are inherited in an autosomal dominant manner, likely through haploinsufficiency. At least one study has reported dominant negative effects of abnormal FOXP1 protein product impacting both wild type FOXP1 and FOXP2 protein translocation into the nucleus (Lozano et al. 2015).

Testing Strategy

This test involves bidirectional Sanger sequencing using genomic DNA of exons 6-21 (most inclusive coding transcript) of the FOXP1 gene plus ~10 bp of flanking non-coding DNA on each side. We will also sequence any single exon (Test #100) in patients with a known pathogenic variant or to confirm research results.

Indications for Test

Individuals presenting with expressive speech impairment as well as characteristic facial features such as broad forehead, down-slanting or narrow palpebral fissures, short nose with a broad tip, macrocephaly, hair upsweep, and prominent fingertip pads are potential candidates for this test. Of note, all FOXP1 variants described in which parental DNA was tested revealed the variants occurred de novo, therefore testing with parental samples is highly recommended (Lozano et al. 2015).


Official Gene Symbol OMIM ID
FOXP1 605515
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Autism Spectrum Disorders and Intellectual Disability (ASD-ID) Comprehensive Sequencing Panel with CNV Detection


Genetic Counselors
  • Bourgeron T. 2016. Comptes Rendus Biologies. 339: 300-7. PubMed ID: 27289453
  • Brown P.J. et al. 2008. Blood. 111: 2816-24. PubMed ID: 18077790
  • Carr C.W. et al. 2010. European Journal of Human Genetics. 18: 1216-20. PubMed ID: 20571508
  • Ferland R.J. et al. 2003. The Journal of Comparative Neurology. 460: 266-79. PubMed ID: 12687690
  • Hamdan F.F. et al. 2010. American Journal of Human Genetics. 87: 671-8. PubMed ID: 20950788
  • Horn D. et al. 2010. Human Mutation. 31: E1851-60. PubMed ID: 20848658
  • Kaufman L. et al. 2010. Journal of Neurodevelopmental Disorders. 2: 182-209. PubMed ID: 21124998
  • Krumm N. et al. 2015. Nature Genetics. 47: 582-8. PubMed ID: 25961944
  • Le Fevre A.K. et al. 2013. American Journal of Medical Genetics. Part A. 161A: 3166-75. PubMed ID: 24214399
  • Levy S.E. et al. 2009. Lancet. 374: 1627-38. PubMed ID: 19819542
  • Lim E.T. et al. 2013. Neuron. 77: 235-42. PubMed ID: 23352160
  • Lozano R. et al. 2015. European Journal of Human Genetics. 23: 1702-7. PubMed ID: 25853299
  • McLaren J., Bryson S.E. 1987. American Journal of Mental Retardation. 92: 243-54. PubMed ID: 3322329
  • McPartland J.C. et al. 2016. Encyclopedia of Mental Health. 2: 124-130
  • Palmesino E. et al. 2010. Plos Biology. 8: e1000446. PubMed ID: 20711475
  • Palumbo O. et al. 2013. Gene. 516: 107-13. PubMed ID: 23287644
  • Pariani M.J. et al. 2009. European Journal of Medical Genetics. 52: 123-7. PubMed ID: 19332160
  • Shu W. et al. 2007. Development. 134: 1991-2000. PubMed ID: 17428829
  • Sztainberg Y, Zoghbi HY. 2016. Nature Neuroscience. 19: 1408-17. PubMed ID: 27786181
  • Teramitsu I. et al. 2004. The Journal of Neuroscience. 24: 3152-63. PubMed ID: 15056695
  • Vissers L.E. et al. 2016. Nature Reviews. Genetics. 17: 9-18. PubMed ID: 26503795
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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