Autism Spectrum Disorders via the TRIP12 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
15403 TRIP12 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15403TRIP1281479 81479(x2) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

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).

TRIP12 (thyroid hormone receptor interactor 12) is an E3 ubiquitin-protein ligase that guards against excessive spreading of ubiquitinated chromatin at sites of DNA damage through an ubiquitin fusion degradation pathway (Lelieveld et al. 2016; Liu et al. 2016; Poulsen et al. 2012). Errors in ubiquitination that result in the accumulation of protein aggregates are well documented in many neurological diseases (Popovic et al. 2014) yet the precise role of TRIP12 in ASD and ID is unknown. The majority of individuals with pathogenic TRIP12 variants present with both ASD and mild to moderate ID (IQ range 53-72), have difficulty falling asleep, and are delayed in speech and language development (O’Roak et al. 2014; Bramswig et al. 2017).

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). While TRIP12 plays a clear role in DNA repair and protein ubiquitination, little is known with respect to neurodevelopment (O’Roak et al. 2014). It appears TRIP12 pathogenic variants lead to ASD/ID symptoms in an autosomal dominant manner, likely through haploinsufficiency (Bramswig et al. 2017).

There are 4 different TRIP12 transcript isoforms that use identical translation start and stop sites, but differ in the usage of internal exons and in-frame splice sites. All transcripts share an identical C-terminal HECT domain, which is characteristic of E3 ubiquitin ligases, but vary in the size of the WWE domain, which mediates protein-protein interactions involving ubiquitin. Thus, the TRIP12 protein ranges between 1,722-2,040 amino acids in length (Bramswig et al. 2017). The majority of affected individuals have a de novo TRIP12 pathogenic variant (nonsense, splice-site, frameshift, or missense) (Wang et al. 2016; Bramswig et al. 2017; O’Roak et al. 2014). Familial missense variants do occur, but with varying penetrance (Bramswig et al. 2017).

Clinical Sensitivity - Sequencing with CNV PG-Select

Currently, the contribution of de novo and inherited factors to ASD risk is estimated to be approximately 50-60% (Krumm et al. 2015). TRIP12 is categorized as a ‘strong candidate’ for ASD in the Simons Foundation Autism Research Initiative (SFARI) Database (https://gene.sfari.org/GeneDetail/TRIP12). However, more than 700 genes have been associated with ASD features (Bourgeron 2016). Based on recent large whole exome sequencing studies, causative variants in TRIP12 were identified in approximately 1/500 to 1/900 ASD probands (Wang et al. 2016; O’Roak et al. 2014).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the TRIP12 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.

Indications for Test

Individuals with family members having known TRIP12 variants and/or displaying ASD-like features with mild to moderate intellectual disability are good candidates for this test.

Gene

Official Gene Symbol OMIM ID
TRIP12 604506
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Mental Retardation, Autosomal Dominant 49 AD 617752

Citations

  • Bourgeron T. 2016. Comptes Rendus Biologies. 339: 300-7. PubMed ID: 27289453
  • Bramswig N.C. et al. 2017. Human Genetics. 136: 179-192. PubMed ID: 27848077
  • Center for Disease Control and Prevention. 2014. Morbidity and Mortality Weekly Report. 63: 1-21. PubMed ID: 24670961
  • Iossifov I. et al. 2014. Nature. 515: 216-21. PubMed ID: 25363768
  • Karam S.M. et al. 2015. American Journal of Medical Genetics. Part A. 167: 1204-14. PubMed ID: 25728503
  • 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
  • Lelieveld S.H. et al. 2016. Nature Neuroscience. 19: 1194-6. PubMed ID: 27479843
  • Levy S.E. et al. 2009. Lancet. 374: 1627-38. PubMed ID: 19819542
  • Liu X. et al. 2016. Febs Letters. 590: 4213-4222. PubMed ID: 27800609
  • McPartland JC et al. 2016. Encyclopedia of Mental Health. 2: 124-130.
  • O'Roak B.J. et al. 2014. Nature Communications. 5: 5595. PubMed ID: 25418537
  • Popovic D. et al. 2014. Nature Medicine. 20: 1242-53. PubMed ID: 25375928
  • Poulsen E.G. et al. 2012. Plos One. 7: e50548. PubMed ID: 23209776
  • 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

loading Loading... ×

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: $
×
Copy Text to Clipboard
×