X-linked Intellectual Disability via the DLG3 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
9871 DLG3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9871DLG381479 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. If the Sanger option is selected, CNV detection may be ordered through Test #600.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Intellectual Disability (ID) is a heterogeneous group of neurodevelopmental disorders, characterized by congenital limitation in intellectual functioning (intelligence quotient, IQ ≤70), and adaptive behavior. It is diagnosed in ~1–3% of the population before 18 years of age (American Association of Intellectual and Developmental Disabilities, AAIDD). X-linked Intellectual Disability (XLID) contributes almost 10-15% of (ID) cases in males.

Deficiency of synapse-associated protein 102 (SAP102) leads to X-linked Mental Retardation-90 (MRX90). The clinical features of MRX90 are variable from nonsyndromic to syndromic and may include (but may not be limited to) delayed psychomotor development, delayed speech development, limited speech, mild to severe ID, learning disability, seizures, obesity, behavioral problems (anxiety, attention-deficit hyperactivity disorder), muscular hypotonia, narrow-thorax, enuresis and abnormalities of the head and neck, including dysmorphic features such as high-arched palate, molar hypoplasia, short and upslanting palpebral fissures and strabismus (Tarpey et al. 2004. PubMed ID: 15185169; Philips et al. 2014. PubMed ID: 24721225; Kumar et al. 2016. PubMed ID: 27222290; Hu et al. 2016. PubMed ID: 25644381). Some carrier females have been observed with mild intellectual disability and seizures, although a random X-inactivation pattern has been reported in the majority of the female carriers (Tarpey et al. 2004. PubMed ID: 15185169; Gieldon et al. 2017. PubMed ID: 28777483).

Genetics

Pathogenic variants in the human Discs large Drosophila homolog of 3 gene (DLG3) lead to MRX90. DLG3 maps to chromosome Xq13.1 and consists of 19 coding exons that translate into an 817 amino acid polypeptide of synapse-associated protein 102 (SAP102). SAP102, a member of the membrane-associated guanylate kinase (MAGUK) protein family, consists of three tandem PDZ domains, one src-homology (SH3) domain and one guanylate kinase (GK) domain. SAP102 is the major MAGUK expressed in the neurons during early brain development and is presumed to participate in early stages of NMDA receptor processing, and clustering and targeting of NMDA receptors in the postsynaptic density (PSD) of excitatory synapses (Tarpey et al. 2004. PubMed ID: 15185169). To date, several pathogenic variants (missense, nonsense, splice site, small frameshift deletions and duplications) have been reported, including two gross deletions/duplications involving DLG3 (Human gene Mutation database). The disease transmission pattern is primarily X-linked recessive.

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect pathogenic variants in <0.1% of individuals with intellectual disability (ID). In this context, it is important to note that although pathological variants over 800 genes have been identified in individuals with ID, a genetic diagnosis is still lacking in most cases due to extreme clinical and genetic heterogeneity of the condition (Vissers et al. 2016. PubMed ID: 26503795). Analytical sensitivity should be high because the majority of pathogenic variants reported within this gene to date are detectable by sequencing.

To date, two gross deletions/duplications involving DLG3 have been reported (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the DLG3 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

This test is primarily implicated for the patients with ID who are negative for any kind of cytogenetic abnormalities, copy number variations, Fragile-X syndrome and also for the family members of the patients who have DLG3 pathogenic variants. Prenatal diagnosis is possible, if the genetic diagnosis has been firmly established in an affected family member.

Gene

Official Gene Symbol OMIM ID
DLG3 300189
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Mental Retardation, X-Linked 90 XL 300850

Citations

  • Gieldon et al. 2017. PubMed ID: 28777483
  • Hu et al. 2016. PubMed ID: 25644381
  • Human Gene Mutation Database (Bio-base).
  • Kumar et al. 2016. PubMed ID: 27222290
  • Philips et al. 2014. PubMed ID: 24721225
  • Tarpey et al. 2004. PubMed ID: 15185169
  • Vissers et al. 2016. PubMed ID: 26503795

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.

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

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ORDER OPTIONS

View Ordering Instructions

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.

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