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Syndromic Intellectual Disability via the PIGY 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
9253 PIGY 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9253PIGY81479 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

  • Renee Bend, PhD

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).

Hyperphosphatasia with mental retardation syndrome 6 (HPMRS6) is a form of syndromic ID caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. The clinical features are variable, and in severe forms death may occur (Ilkovski et al. 2015. PubMed ID: 26293662). Individuals with HPMRS6 may present with global developmental delay, developmental regression, dysmorphic features, hypotonia, seizures, congenital cataracts, and anomalies of the abdominal, skeletal, genitourinary, dental, cardiac and muscular systems. Biochemical abnormalities include increased serum alkaline phosphatase, increased serum creatine kinase and decreased expression of GPI-anchored proteins (CD55 and CD59) on fibroblasts (Ilkovski et al. 2015. PubMed ID: 26293662).

Genetics

Hyperphosphatasia with mental retardation syndrome 6 (HPMRS6) is an autosomal recessive disorder caused by pathogenic variants in human ‘Phosphatidylinositol Glycan Anchor Biosynthesis Class Y Protein’ gene (PIGY). PIGY maps to chromosome 4q22.1 and consists of one coding exon that translates into the 71 amino acid polypeptide PIGY. PIGY is a part of the GPI-N-acetylglucosaminyltransferase (GIP-GnT) complex, required for the biosynthesis of glycosylphosphatidylinositol (GPI). GPI is synthesized within the endoplasmic reticulum and serves as an anchor for many surface proteins, implicated in cell-cell interactions. To date, only two pathogenic variants (one missense and one in the regulatory region) have been reported in human PIGY, and there is no report of any gross deletion/duplication that includes PIGY.

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 all pathogenic variants reported within this gene to date are detectable by sequencing.

Testing Strategy

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

This test is primarily implicated for the patients with intellectual disabilities 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 known PIGY pathogenic variants. Prenatal diagnosis is possible, if the genetic diagnosis has been firmly established in an affected family member. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PIGY.

Gene

Official Gene Symbol OMIM ID
PIGY 610662
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Hyperphosphatasia with Mental Retardation Syndrome 6 AR 616809

Citations

  • Ilkovski et al. 2015. PubMed ID: 26293662
  • 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.
  • 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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