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Autism Spectrum Disorders/Intellectual Disability via the MED13 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
12083 MED13 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
12083MED1381479 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 disorder (ASD) and intellectual disability (ID) are heterogeneous groups of neurodevelopmental disorders. ASD is characterized by varying degrees of social impairment, communication ability, propensity for repetitive behavior(s), and restricted interests (Levy et al. 2009. PubMed ID: 19819542); whereas ID 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, irrespective of social class and culture (Kaufman et al. 2010. PubMed ID: 21124998; Vissers et al. 2016. PubMed ID: 26503795). In contrast, ASD symptoms usually present by age 3, and diagnosis is based on the degree and severity of symptoms and behaviors (McPartland et al. 2016). ASDs and ID are highly comorbid, suggesting shared etiologies in many forms. For ASD specifically, comorbidities have been observed in more than 70% of cases, and include ID, epilepsy, language deficits, and gastrointestinal problems (Sztainberg and Zoghbi. 2016. PubMed ID: 27786181). 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 and ID (Bourgeron. 2016. PubMed ID: 27289453).

Pathogenic variants in MED13 have been implicated in the development of ASD and ID phenotypes. All individuals present with developmental delay, intellectual disability, speech delay or speech anomalies of varying severity. The majority of patients also display gross motor development, and eye or vision anomalies. Dysmorphic features include widely spaced eyes, narrow palpebral fissures, broad/high nasal bridge, full nasal tip, synophrys, flat philtrum, thin upper lip, and wide mouth. Minor features include attention-deficit hyperactivity disorder, a formal diagnosis of ASD (~40%), delayed fine motor development, hypotonia, myoclonic epilepsy, Duane anomaly, strabismus, nystagmus, visual impairment, optic nerve abnormalities, hearing loss, heart defects, and chronic obstipation (Snijders Blok et al. 2018. PubMed ID: 29740699).

Genetics

Genetic aberrations are reported to be responsible for 50%-90% and 15%-50% of ASD and ID cases, respectively. 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 (Centers for Disease Control and Prevention. 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).

MED13 pathogenic variants result in ASD and ID symptoms in an autosomal dominant manner, as nearly all reported individuals are heterozygous for de novo missense or loss-of-function (nonsense, frameshift) variants. At least one report of an inherited MED13 nonsense variant from an affected parent has been documented in the literature.

The human MED13 gene contains 30 protein-coding exons which encode a 2,174 amino acid protein. The MED13 protein includes an N-terminal domain (residues 11-383) encoding a phosphodegron motif involved in protein degradation as well as a C-terminal domain (residue 1640-2163) with unspecified function. While phenotype-genotype correlations have not been reported, the majority or reported pathogenic variants cluster within the N- and C- terminal domains (Snijders Blok et al. 2018. PubMed ID: 29740699).

MED13 (mediator complex subunit 13) encodes a component of the CDK8 regulatory subunit of the Mediator complex. The Mediator complex is a necessary for the formation of the pre-initiation complex and stable RNA polymerase II-dependent transcriptional activity. MED13 degradation via ubiquitination is believed to be the mechanism by which CDK8-dependent Mediator activity is regulated within the cell (Snijders Blok et al. 2018. PubMed ID: 29740699). Disruption of Mediator and CDK8-regulatory protein subunits have also been implicated in other neurodevelopmental disorder phenotypes (Donnio et al. 2017. PubMed ID: 28369444; Vulto-van Silfhout et al. 2013. PubMed ID: 23395478).

Clinical Sensitivity - Sequencing with CNV PGxome

Genetic variants have been found responsible in 25-50% of intellectual disability cases, and this percentage increases proportionally with the severity of the phenotype (McLaren and Bryson. 1987. PubMed ID: 3322329). For autism spectrum disorder (ASD), while heritability estimates have been reported as high as 90% (Bailey et al. 1995. PubMed ID: 7792363; Lichtenstein et al. 2010. PubMed ID: 20686188), only 20% of ASD cases can be explained to date using genetic approaches (Devlin and Scherer. 2012. PubMed ID: 22463983).

While MED13 is categorized as a gene with ‘syndromic, strong evidence’ regarding its association with ASD in the Simons Foundation Autism Research Initiative (SFARI) Database (https://gene.sfari.org/database/human-gene/MED13), no single gene has been reported to account for more than 1% of all ASD cases to date (Hoang et al. 2018. PubMed ID: 28803755). Furthermore, large cohort studies of individuals with neurodevelopmental phenotypes have implicated hundreds of genes (Larsen et al. 2016. PubMed ID: 27790361; Bourgeron. 2016. PubMed ID: 27289453). Therefore, the clinical sensitivity of any single gene test with regard to a neurodevelopmental phenotype is expected to be low (less than or equal to 1%).

Testing Strategy

This test provides full coverage of all coding exons of the MED13 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

The vast majority of reported missense and loss-of-function variants in MED13 are de novo in nature. However, individuals with family members having known MED13 variants and/or presenting with ID developmental delay, speech abnormalities, vision abnormalities, or defects in gross motor development with various dysmorphic features are candidates for this test.

Gene

Official Gene Symbol OMIM ID
MED13 603808
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Intellectual developmental disorder 61 AD 618009

Citations

  • Bailey et al. 1995. PubMed ID: 7792363
  • Bourgeron. 2016. PubMed ID: 27289453
  • Centers for Disease Control and Prevention. 2014. PubMed ID: 24670961
  • Devlin and Scherer. 2012. PubMed ID: 22463983
  • Donnio et al. 2017. PubMed ID: 28369444
  • Hoang et al. 2017. PubMed ID: 28803755
  • Iossifov et al. 2014. PubMed ID: 25363768
  • Karam et al. 2015. PubMed ID: 25728503
  • Kaufman et al. 2010. PubMed ID: 21124998
  • Larsen et al. 2016. PubMed ID: 27790361
  • Levy et al. 2009. PubMed ID: 19819542
  • Lichtenstein et al. 2010. PubMed ID: 20686188
  • McLaren and Bryson. 1987. PubMed ID: 3322329
  • McPartland. 2016. Encyclopedia of Mental Health.
  • Snijders Blok et al. 2018. PubMed ID: 29740699
  • Sztainberg and Zoghbi. 2016. PubMed ID: 27786181
  • Vissers et al. 2016. PubMed ID: 26503795
  • Vulto-van Silfhout et al. 2013. PubMed ID: 23395478

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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