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Autism Spectrum Disorders via the DSCAM Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
5409 DSCAM 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
5409DSCAM81479 81479,81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Greg Fischer, PhD

Clinical Features and Genetics

Clinical Features

Autism Spectrum Disorders (ASD) include several neurodevelopmental disorders characterized by varying degrees of social impairment, communication ability, and propensity for restricted interests and repetitive behavior(s) (Levy et al. 2009). ASD usually presents by age 3. Diagnosis is based on the degree and severity of symptoms and behaviors (Diagnostic and Statistical Manual of Mental Disorders (DSM-5); 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). Recent studies using whole exome trio studies have identified novel gene candidates, with familial and de novo variants from several hundred genes now implicated in the development of ASD (Bourgeron 2016).

Genetics

Genetic aberrations are reported to be responsible for 50%-90% and 15%-50% of ASD and ID cases, respectively, and inheritance overall is multifactorial (Larsen et al. 2016; Karam et al. 2015). Incidence of ASD is approximately 1 in 68 individuals with a male-to-female ratio of 4:1 (Center for Disease Control 2014). De novo missense and likely gene disrupting variants are 15% and 75% more frequent in ASD patients than unaffected controls, respectively (Iossifov et al. 2014).

DSCAM (down syndrome cell adhesion molecule) is a neuronal cell adhesion molecule with homology to members of the immunoglobulin superfamily. DSCAM is expressed in most neuronal cells and functions in neuron generation and growth, dendrite self/non-self recognition, and synapse formation and plasticity (Jia et al. 2011). DSCAM is located in chromosome region 21q22.2-q22.3 within the Down syndrome (DS) critical region (DSCR). This region includes genes that, because of increased dosage, are believed to result in the clinical phenotypes of DS (Jia et al. 2011). Known targets of DSCAM are p21-associated kinases (PAKs) which mediate neuron cytoskeletal organization, morphogenesis, and synaptic plasticity via DSCAM activation (Kreis and Barnier 2009; Pérez-Núñez et al. 2016).

The human DSCAM gene contains 33 protein-coding exons which encode a 2,012 amino acid protein. DSCAM alternative splicing is extensive in non-vertebrates (such as arthropods) and is believed to contribute to neuron self/non-self recognition. However, vertebrate genomes encode only two DSCAM homologs (DSCAM & DSCAML1) and neither is reported to be alternatively spliced to as significant an extent (Hattori et al. 2008; Schmucker and Chen 2009). The human DSCAM protein contains 10 Ig domains and 6 fibronectin type III repeats (Schmucker and Chen 2009). At least 6 de novo loss-of-function variants have been reported in individuals presenting with ASD features from multiple ASD cohorts (Iossifov et al. 2014; DeRubeis et al. 2014; Wang et al. 2016), supporting an autosomal dominant mode of inheritance.

Clinical Sensitivity - Sequencing with CNV PGxome

Currently, the contribution of de novo and inherited factors to ASD risk is estimated to be approximately 50-60% (Krumm et al. 2015). DSCAM is categorized as a gene with ‘high confidence’ regarding its susceptibility for ASD in the Simons Foundation Autism Research Initiative (SFARI) Database (https://gene.sfari.org/GeneDetail/DSCAM). However, more than 700 genes have been associated with ASD features (Bourgeron 2016). Based on large whole exome sequencing studies, de novo loss-of-function variants in DSCAM were identified in approximately 6/6,300 individuals from multiple ASD cohorts (Iossifov et al. 2014; De Rubeis et al. 2014; Wang et al. 2016). Recent investigations identified 2 additional ASD individuals with de novo likely gene disrupting variants in DSCAM from a cohort of 13,407 trios (Stessman et al. 2017).

Testing Strategy

This test provides full coverage of all coding exons of the DSCAM gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Reported variants in DSCAM are almost exclusively de novo loss-of-function in nature. However, individuals with family members having known DSCAM variants and/or presenting with idiopathic ASD features are candidates for this test.

Gene

Official Gene Symbol OMIM ID
DSCAM 602523
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID

Citations

  • Bourgeron T. 2016. Comptes Rendus Biologies. 339: 300-7. PubMed ID: 27289453
  • Center for Disease Control and Prevention. 2014. Morbidity and Mortality Weekly Report. Surveillance Summaries (Washington, D.C. : 2002). 63: 1-21. PubMed ID: 24670961
  • De Rubeis S. et al. 2014. Nature. 515: 209-15. PubMed ID: 25363760
  • Hattori D. et al. 2008. Annual Review of Cell and Developmental Biology. 24: 597-620. PubMed ID: 18837673
  • Iossifov I. et al. 2014. Nature. 515: 216-21. PubMed ID: 25363768
  • Jia Y.L. et al. 2011. Neuroscience Letters. 491: 153-7. PubMed ID: 21241773
  • Karam S.M. et al. 2015. American Journal of Medical Genetics. Part A. 167: 1204-14. PubMed ID: 25728503
  • Kreis P., Barnier J.V. 2009. Cellular Signalling. 21: 384-93. PubMed ID: 19036346
  • Krumm N. et al. 2015. Nature Genetics. 47: 582-8. PubMed ID: 25961944
  • Larsen E. et al. 2016. Molecular Autism. 7: 44. PubMed ID: 27790361
  • Levy S.E. et al. 2009. Lancet. 374: 1627-38. PubMed ID: 19819542
  • McPartland J.C. et al. 2016. Encyclopedia of Mental Health. 2: 124-130.
  • Pérez-Núñez R. et al. 2016. Neurotoxicity Research. 30: 76-87. PubMed ID: 26966010
  • Schmucker D., Chen B. 2009. Genes & Development. 23: 147-56. PubMed ID: 19171779
  • Stessman H.A. et al. 2017. Nature Genetics. 49: 515-526. PubMed ID: 28191889
  • Sztainberg Y., Zoghbi H.Y. 2016. Nature Neuroscience. 19: 1408-17. PubMed ID: 27786181
  • Wang et al. 2016. PubMed ID: 27824329

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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