Glaucoma Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10335 ATOH7 81479,81479 Order Options and Pricing
COL4A1 81408,81479
COL8A1 81479,81479
COL8A2 81479,81479
CYP1B1 81404,81479
FOXC1 81479,81479
FOXE3 81479,81479
LMX1B 81479,81479
LTBP2 81479,81479
MAF 81479,81479
MFRP 81479,81479
MYOC 81479,81479
OPTC 81479,81479
OPTN 81406,81479
PAX6 81479,81479
PITX2 81479,81479
PXDN 81479,81479
SH3PXD2B 81479,81479
SIX6 81479,81479
SLC4A4 81479,81479
TEK 81479,81479
WDR36 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10335Genes x (22)81479 81404, 81406, 81408, 81479 $960 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

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

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

Clinical Features

Glaucoma is a major cause of blindness worldwide. Glaucoma is characterized by elevated intraocular pressure (IOP), increased corneal diameter (megalocornea), enlarged globe (buphthalmos), Haab’s striae (opacification of the cornea with ruptures involving Descemet’s membrane), corneal edema and optic nerve head cupping, thinning of the anterior sclera and atrophy of the iris. Symptoms include photophobia, blepharospasm (abnormal contraction of the eyelid), and hyperlacrimation (excessive tearing). Abnormal development of the anterior segment angle or goniodysgenesis are the hallmarks of congenital glaucoma (Abu-Amero et al. 2011. PubMed ID: 22128238).

Primary congenital glaucoma (PCG) or Trabeculodysgenesis presents in neonates and during the infantile period with a varying prevalence rate ranging from 1 in 1,250 to 20,000 among different geographic locations and ethnic groups. The highest prevalence is found in the Gypsy population of Slovakia (1 in 1,250) followed by Saudi Arabians (1:2,500), Southern India (1:3,300), and the Western nations (1:5000-22,000) (Gencik et al. 1982. PubMed ID: 7173860; Azmanov et al. 2011. PubMed ID: 21081970; Abu-Amero. 2011. PubMed ID: 22128238).

Adult-onset Primary open-angle glaucoma (POAG) is the most common subtype affecting all ages, for which there is currently no cure, only treatments that may slow its progress. Early detection is needed in order to prevent vision loss (Martin et al. 2000. PubMed ID: 10851252; Abu-Amero. 2011. PubMed ID: 22128238).

With the advent of gene therapy and other types of treatments, the identification of causative genes and variants is becoming increasingly important.

Please see the following links for clinical trials and management options:

https://medlineplus.gov/glaucoma.html

Glaucoma Clinical trials

Genetics

Pathogenic variants in CYP1B1, and LTBP2 have been reported to cause primary congenital glaucoma with autosomal recessive inheritance (Abu-Amero. 2011. PubMed ID: 22128238). A study indicated that the CYP1B1 c.182G>A (p.Gly61Glu) variant was seen in 78% of the PCG chromosomes analyzed and reported as a common mutation in Saudi Arabian population (Bejjani et al. 1998. PubMed ID: 9463332, reported as 3987G>A change). CYP1B1 c.1159G>A (p.Glu387Lys) is a common pathogenic variant in Slovak Gypsies (Roms) due to a founder effect (Plásilová et al. 1999. PubMed ID: 10227395). Both these variants are reported at ~0.003% in the general population (https://gnomad.broadinstitute.org/variant/2-38302350-C-T; https://gnomad.broadinstitute.org/variant/2-38298338-C-T).

Juvenile-onset POAG exhibits autosomal dominant inheritance and is due to heterozygous pathogenic variants in MYOC, OPTN, TEK or WDR36. Adult-onset POAG is generally inherited as a complex trait with multigenic inheritance (Ray and Mookherjee. 2009. PubMed ID: 20090207; Carnes et al. 2014. PubMed ID: 24875647). Approximately 10%–20% of adult-onset POAG cases are due to monoallelic pathogenic variants in the MYOC gene (Khan. 2011. PubMed ID: 21730848; Wiggs et al. 2004. PubMed ID: 15108121).

Glaucoma is manifested in several syndromic disorders associated with anterior segment dysgenesis. Examples include Nail-patella syndrome, Axenfeld-Rieger syndrome, Aniridia, nanophthalmos, and Frank-ter Haar syndrome. Causative variants in LMX1B (Vollrath et al. 1998. PubMed ID: 9618165), PITX2 (Strungaru et al. 2007. PubMed ID: 17197537), FOXC1 also known as FKHL7 (Ito et al. 2014. PubMed ID: 24556684; Paylakhi et al. 2013. PubMed ID: 23541832), FOXE3 (Semina et al. 2001. PubMed ID: 11159941), PAX6 (Tzoulaki et al. 2005. PubMed ID: 15918896), MAF (Anand et al. 2018. PubMed ID: 29314435) and COL4A1 (Sibon et al. 2007. PubMed ID: 17696175) are inherited in an autosomal dominant manner. Causative variants in MFRP (Ayala-Ramirez et al. 2006. PubMed ID: 17167404), SH3PXD2B (Iqbal. 2010. PubMed ID: 20137777), SLC4A4 (Igarashi et al. 1999. PubMed ID: 10545938), SIX6 (Carnes et al. 2014. PubMed ID: 24875647) and ATOH7 (Prasov et al. 2012. PubMed ID: 22645276) are inherited in an autosomal recessive manner. The mode of inheritance for OPTC (Acharya et al. 2007. PubMed ID: 17359525), COL8A2 and COL8A1 (Desronvil et al. 2010. PubMed ID: 21139683) is currently unknown.

Of note, de novo variants in MYOC and FOXC1 have been documented to be causative for glaucoma (Kuchtey et al. 2013. PubMed ID: 23517641; Wiggs and Pasquale. 2017. PubMed ID: 28505344).

Human and experimental models suggest that elevated intraocular pressure (IOP) obstructs retrograde and anterograde axonal transport of neurotrophins in retinal ganglion cells (RGCs) and results in RGCs axon damage within the optic nerve head (ONH) (Stowell et al. 2017. PubMed ID: 28223180; Chitranshi et al. 2018. PubMed ID: 29676228).

A wide variety of causative variants (missense, nonsense, splicing, small deletions and insertions) have been reported in these glaucoma-associated genes, including large deletions/duplications and complex genomic rearrangements in a few genes (FOXC1, PAX6, CYP1B1, PITX2, LMX1B, SHH, MAF, TEK and ATOH7) (Human Gene Mutation Database). All documented large deletions in OPTN have been reported in amyotrophic lateral sclerosis patients, while none have been reported in glaucoma patients (Human Gene Mutation Database).

See individual gene summaries for more information on molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

Abu-Amero et al. detected CYP1B1 pathogenic variants in 76% of families (41 out of 54) with at least one affected member with primary congenital glaucoma (PCG) (Abu-Amero. 2011. PubMed ID: 22128238). Another molecular analysis of CYP1B1 identified three pathogenic variants in 78% (7/9) of the unrelated PCG index cases (El-Gayar et al. 2009. PubMed ID: 19597567). Approximately 10%–20% of adult-onset primary open-angle glaucoma (POAG) cases are due to pathogenic variants in the MYOC gene (Khan. 2011. PubMed ID: 21730848; Wiggs et al. 2004. PubMed ID: 15108121). Another study reported that 3.6% (9/251) of the POAG patients had pathogenic variants in the CYP1B1, MYOC, and OPTN genes (Kumar et al. 2007. PubMed ID: 17563717).

Testing Strategy

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

This panel typically provides 99.5% coverage of all coding exons of the genes 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 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

All patients with symptoms suggestive of primary open angle, congenital, juvenile, or adult-onset glaucoma are candidates.

Genes

Official Gene Symbol OMIM ID
ATOH7 609875
COL4A1 120130
COL8A1 120251
COL8A2 120252
CYP1B1 601771
FOXC1 601090
FOXE3 601094
LMX1B 602575
LTBP2 602091
MAF 177075
MFRP 606227
MYOC 601652
OPTC 605127
OPTN 602432
PAX6 607108
PITX2 601542
PXDN 605158
SH3PXD2B 613293
SIX6 606326
SLC4A4 603345
TEK 600221
WDR36 609669
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Aortic Aneurysm, Familial Thoracic 11, susceptibility to AD 617349
Aphakia, Congenital Primary AR 610256
Axenfeld-Rieger Syndrome Type 3 AD 602482
Axenfeld-Rieger syndrome, type 1 AD 180500
Ayme-Gripp Syndrome AD 601088
Cataract 21 AD 610202
Cataract 34, multiple types 612968
Coloboma Of Optic Disc AD 120430
Coloboma, Ocular AD 120200
Congenital Aniridia AD 106210
Corneal Dystrophy Fuchs Endothelial 1 AD 136800
Corneal Dystrophy, Posterior Polymorphous, 2 AD 609140
Corneal Opacification and Other Ocular Anomalies AR 269400
Foveal Hypoplasia And Presenile Cataract Syndrome AD 136520
Frank Ter Haar Syndrome AR 249420
Glaucoma 1, Open Angle, G AR 609887
Glaucoma 3, Primary Congenital, D AR 613086
Glaucoma 3, primary congenital, E AD 617272
Glaucoma, Congenital AR 231300
Glaucoma, Normal Tension, Susceptibility To AD 606657
Iridogoniodysgenesis Type1 AD 601631
Iridogoniodysgenesis, Dominant Type AD 137600
Keratitis, Hereditary AD 148190
Microphthalmia, Isolated 5 AR 611040
Microspherophakia and/or Megalocornea, with Ectopia Lentis and with or without Secondary Glaucoma AR 251750
Nail-Patella Syndrome AD 161200
Nanophthalmos 2 AR 609549
Optic Disc Anomalies with Retinal and/or Macular Dystrophy AR 212550
Optic Nerve Hypoplasia, Bilateral AD 165550
Persistent Hyperplastic Primary Vitreous, Autosomal Recessive AR 221900
Peters Anomaly AD 604229
Porencephaly 1 175780
Primary Open Angle Glaucoma AD 137760
Primary Open Angle Glaucoma Juvenile Onset 1 AD 137750
Renal Tubular Acidosis, Proximal, With Ocular Abnormalities And Mental Retardation AR 604278
Ring Dermoid Of Cornea AD 180550
Weill-Marchesani Syndrome 3 AR 614819

Related Test

Name
PGxome®

Citations

  • Abu-Amero. 2011. PubMed ID: 22128238
  • Acharya et al. 2007. PubMed ID: 17359525
  • Anand et al. 2018. PubMed ID: 29314435
  • Ayala-Ramirez et al. 2006. PubMed ID: 17167404
  • Azmanov et al. 2011. PubMed ID: 21081970
  • Bejjani et al. 1998. PubMed ID: 9463332
  • Carnes et al. 2014. PubMed ID: 24875647
  • Chitranshi et al. 2018. PubMed ID: 29676228
  • Desronvil et al. 2010. PubMed ID: 21139683
  • El-Gayar et al. 2009. PubMed ID: 19597567
  • Gencik et al. 1982. PubMed ID: 7173860
  • Human Gene Mutation Database (Bio-base).
  • Igarashi. 1999. PubMed ID: 10545938
  • Iqbal. 2010. PubMed ID: 20137777
  • Ito et al. 2014. PubMed ID: 24556684
  • Khan. 2011. PubMed ID: 21730848
  • Kuchtey et al. 2013. PubMed ID: 23517641
  • Kumar et al. 2007. PubMed ID: 17563717
  • Martin et al. 2000. PubMed ID: 10851252
  • Paylakhi et al. 2013. PubMed ID: 23541832
  • Plásilová et al. 1999. PubMed ID: 10227395
  • Prasov et al. 2012. PubMed ID: 22645276
  • Ray and Mookherjee. 2009. PubMed ID: 20090207
  • Semina et al. 2001. PubMed ID: 11159941
  • Sibon et al. 2007. PubMed ID: 17696175
  • Stowell et al. 2017. PubMed ID: 28223180
  • Strungaru et al. 2007. PubMed ID: 17197537
  • Tzoulaki et al. 2005. PubMed ID: 15918896
  • Vollrath et al. 1998. PubMed ID: 9618165
  • Wiggs and Pasquale. 2017. PubMed ID: 28505344
  • Wiggs et al. 2004. PubMed ID: 15108121

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

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

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