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Posterior Microphthalmia via the PRSS56 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
8393 PRSS56 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8393PRSS5681479 81479(x2) $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

  • Dana Talsness, PhD

Clinical Features and Genetics

Clinical Features

Posterior microphthalmos (MCOP) is a relatively rare, isolated malformation of the eye. Clinically, MCOP is characterized by extreme hyperopia, retinal folding, normal anterior segment with a small posterior segment, steep corneal curvatures, shallow anterior chamber, thick lenses and scleral wall, reduced visual acuity and strabismic amblyopia. Funduscopy findings include crowded optical discs, tortuous vessels, and an abnormal foveal avascular zone. Affected individuals are at-risk for narrow-angle glaucoma, chorioretinal pathology including uveal effusion and amblyopia due to the abnormally small eye size (Hmani-Aifa et al. 2009; Gal et al. 2011; Said et al. 2013).

Genetics

To date, pathogenic variants in two genes MFRP (encodes membrane frizzled-related protein) and PRSS56 (encodes a serine protease) have been reported to be causative for autosomal recessive Posterior microphthalmia (arMCOP) (Said et al. 2013).

PRSS56, which encodes a trypsin-like serine protease, is classified as a member of the chymotrypsin family as the encoded protein carries a highly conserved triad consisting of Asp191-His145-Ser286 (similar to trypsin triad Asp102-His57-Ser195), which is required for the catalytic activity of the protein (Gal et al. 2011).

MCOP was found to be highly prevalent in the Faroe Islands due to a founder effect (carrier frequency 3.2%). Patients of the Faroese families were either homozygous for c.926G>C (p.Trp309Ser) or compound heterozygous for c.926G>C and c.526C>G (p.Arg176Gly) variants in PRSS56. Molecular modeling of the p.Trp309Ser variant showed substantially reduced enzyme affinity and reactivity toward in vivo protein substrates. A homozygous single nucleotide deletion c.1066dupC was identified in five arMCOP patients from a consanguineous Tunisian family, which is predicted to result in translational frameshift and protein truncation (p.Gln356Argfs*148). In the Saudi population, PRSS56 pathogenic variants were shown to be the major cause of arMCOP (Orr et al. 2011; Gal et al. 2011; Said et al. 2013; Nowilaty et al. 2013). So far, over 20 pathogenic variants (missense variants and single nucleotide duplications) have been reported in the PRSS56 gene, which the majority are missense variants (90%) (Human Gene Mutation Database; Orr et al. 2011; Gal et al. 2011).

Clinical Sensitivity - Sequencing with CNV PGxome

In a mutational screening of 25 MCOP affected patients from 13 families, 19 Saudi patients (~75%) were homozygous for PRSS56 mutations, 1 Indian and 1 Saudi patient had mutations in MFRP, and in 4 Saudi patients no causative variants were detected. All patients had a similar phenotype (Nowilaty et al. 2013).

Testing Strategy

This test provides full coverage of all coding exons of the PRSS56 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

All patients with symptoms suggestive of posterior segment anomalies are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PRSS56.

Gene

Official Gene Symbol OMIM ID
PRSS56 613858
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Microphthalmia, Isolated 6 AR 613517

Citations

  • Gal A, Rau I, El Matri L, Kreienkamp H-J, Fehr S, Baklouti K, Chouchane I, Li Y, Rehbein M, Fuchs J, Fledelius HC, Vilhelmsen K, Schorderet DF, Munier FL, Ostergaard E, Thompson DA, Rosenberg T. 2011. Autosomal-Recessive Posterior Microphthalmos Is Caused by Mutations in PRSS56, a Gene Encoding a Trypsin-Like Serine Protease. The American Journal of Human Genetics 88: 382–390. PubMed ID: 21397065
  • Hmani-Aifa M, Salem S Ben, Benzina Z, Bouassida W, Messaoud R, Turki K, Khairallah M, Rebaï A, Fakhfekh F, Söderkvist P, Ayadi H. 2009. A genome-wide linkage scan in Tunisian families identifies a novel locus for non-syndromic posterior microphthalmia to chromosome 2q37.1. Hum. Genet. 126: 575–587. PubMed ID: 19526372
  • Human Gene Mutation Database (Bio-base).
  • Nowilaty SR, Khan AO, Aldahmesh MA, Tabbara KF, Al-Amri A, Alkuraya FS. 2013. Biometric and molecular characterization of clinically diagnosed posterior microphthalmos. Am. J. Ophthalmol. 155: 361–372.e7. PubMed ID: 23127749
  • Orr A, Dubé M-P, Zenteno JC, Jiang H, Asselin G, Evans SC, Caqueret A, Lakosha H, Letourneau L, Marcadier J, Matsuoka M, Macgillivray C, Nightingale M, Papillon-Cavanagh S, Perry S, Provost S, Ludman M, Guernsey DL, Samuels ME. 2011. Mutations in a novel serine protease PRSS56 in families with nanophthalmos. Molecular vision 17: 1850. PubMed ID: 21850159
  • Said MB, Chouchène E, Salem SB, Daoud K, Largueche L, Bouassida W, Benzina Z, Ayadi H, Söderkvist P, Matri L, Hmani-Aifa M. 2013. Posterior microphthalmia and nanophthalmia in Tunisia caused by a founder c.1059_1066insC mutation of the PRSS56 gene. Gene 528: 288–294. PubMed ID: 23820083

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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