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Autism Spectrum Disorders and CTNND2-Related Disorders via the CTNND2 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
9809 CTNND2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9809CTNND281479 81479,81479 $890 Order Options and Pricing

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).

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. PubMed ID: 19819542). 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. PubMed ID: 27786181). Recent studies using whole exome trios have identified novel gene candidates, with familial and de novo variants from several hundred genes now implicated in the development of ASD (Bourgeron. 2016. PubMed ID: 27289453).

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. PubMed ID: 27790361; Karam et al. 2015. PubMed ID: 25728503). Incidence of ASD is approximately 1 in 68 individuals with a male-to-female ratio of 4:1 (Center for Disease Control 2014. PubMed ID: 24670961). 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. PubMed ID: 25363768).

CTNND2 (delta-Catenin/neural plakophilin-related armadillo-repeat protein/neurojungin) encodes a delta-catenin that interacts with cadherins (cell-cell junction proteins), and in the neuronal context, synapse junction-associated proteins (Lu et al. 2016. PubMed ID: 27380241). CTNND2 also impacts neuronal structure/function and synapse morphogenesis during neuronal development (Lu et al. 2016. PubMed ID: 27380241). Copy number and sequence variation within CTNND2 have been associated with autism spectrum disorder (Turner et al. 2015. PubMed ID: 25807484), as well as other neurological disorders including Alzheimer’s disease (Jun et al. 2012. PubMed ID: 22984439), Cri-du-chat syndrome and intellectual disabilities (Hofmeister et al. 2015. PubMed ID: 25473103; Belcaro et al. 2015. PubMed ID: 25839933, Medina et al. 2000. PubMed ID: 10673328, Sardina et al. 2014. PubMed ID: 24677774), and schizophrenia (Sklar et al. 2008. PubMed ID: 18668038; Stefansson et al. 2008. PubMed ID: 18668039).

Missense variants within CTNND2 at conserved residues were reported to be significantly more frequent in ASD cohorts than controls, however whether these variants arose de novo was not reported (Turner et al. 2015. PubMed ID: 25807484). Furthermore, exon-disrupting copy number variants (CNVs) within CTNND2 are overall enriched in cohorts of individuals generally diagnosed with neurodevelopmental disorders compared to population-based control cohorts. For ASD specifically, exon-disrupting deletions are observed in excess, suggesting a haploinsufficient mechanism for ASD development and an autosomal dominant mode of inheritance (Turner et al. 2015. PubMed ID: 25807484).

Clinical Sensitivity - Sequencing with CNV PGxome

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. PubMed ID: 25961944). CTNND2 is categorized as a ‘strong candidate’ regarding its association with ASD in the Simons Foundation Autism Research Initiative (SFARI) Database (https://gene.sfari.org/database/human-gene/CTNND2). However, more than 700 genes have been associated with ASD features (Bourgeron. 2016. PubMed ID: 27289453), suggesting that the clinical sensitivity of any single gene sequencing or copy number variant test in the context of autism spectrum disorder phenotypes is minimal. With respect to CNVs in probands diagnosed with a neurodevelopmental disorder, 25/19,556 (0.13%) cases had a CNV overlapping with a CTNND2 exonic region compared to 3/13,898 (0.02%) in population-based controls (Odds Ratio: 5.9, p=4.10x10-4) (Turner et al. 2015. PubMed ID: 25807484).

Testing Strategy

This test provides full coverage of all coding exons of the CTNND2 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

Individuals with family members having known CTNND2 variants and/or presenting with neurodevelopmental disorders (including autism spectrum disorder, syndrome and nonsyndromic intellectual disability, and schizophrenia) are potential candidates for this test.

Gene

Official Gene Symbol OMIM ID
CTNND2 604275
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID

Citations

  • Belcaro et al. 2015. PubMed ID: 25839933
  • Bourgeron. 2016. PubMed ID: 27289453
  • Center for Disease Control and Prevention. 2014. Morbidity and Mortality Weekly Report. Surveillance Summaries (Washington, D.C.). 63: 1-21. PubMed ID: 24670961
  • Hofmeister et al. 2015. PubMed ID: 25473103
  • Iossifov et al. 2014. PubMed ID: 25363768
  • Jun et al. 2012. PubMed ID: 22984439
  • Karam et al. 2015. PubMed ID: 25728503
  • Krumm et al. 2015. PubMed ID: 25961944
  • Larsen et al. 2016. PubMed ID: 27790361
  • Levy et al. 2009. PubMed ID: 19819542
  • Lu et al. 2016. PubMed ID: 27380241
  • McPartland et al. 2016. Encyclopedia of Mental Health. 2: 124-130.
  • Medina et al. 2000. PubMed ID: 10673328
  • Sardina et al. 2014. PubMed ID: 24677774
  • Sklar et al. 2008. PubMed ID: 18668038
  • Stefansson et al. 2008. PubMed ID: 18668039
  • Sztainberg and Zoghbi. 2016. PubMed ID: 27786181
  • Turner et al. 2015. PubMed ID: 25807484

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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