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Cataract 9, Multiple Types (CTRCT9) via the CRYAA 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
3879 CRYAA 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3879CRYAA81479 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

  • Jamie Fox, PhD

Clinical Features and Genetics

Clinical Features

Cataract 9, multiple types (CTRCT9) is a common congenital, progressive vision disorder that causes blindness in infants (Litt et al. 1998). It is characterized by the development of blurred and dimmed vision resulting from clouding of the lens (opacification) due to changes in its microarchitecture (Kumar et al. 2013). This particular damage to the lens induces light to scatter as well as proteins to aggregate, thereby resulting in loss of transparency (Hejtmancik 2008). CTRCT9 comprises multiple types of cataracts, which mainly depend on the location within the lens, density or opacity, color, symmetry, and progression (Beby et al. 2007; Shafie et al. 2006). Intrafamilial variability in the morphology and location within the lens commonly occurs in CTRCT9 (Javadiyan et al. 2016). The incidence of congenital cataract has been estimated to be roughly 2.5 per 10,000 live births (Wirth et al. 2002; Yi et al. 2011). Perinatal ocular examination in newborns via red reflex examination is generally conducted using an ophthalmoscope (American Academy of Pediatrics 2002), whereas young children are assessed by slit-lamp microscopy (Li et al. 2013). Congenital cataract is usually treated by surgery and early primary intraocular lens implantation during the first year of life (Ventura et al. 2013).

Genetics

CTRCT9 is an autosomal dominant vision disorder that is caused by pathogenic sequence variants in the crystallin, alpha-a (CRYAA) gene [also known as the crystallin, alpha-1 (CRYA1) and heat-shock protein beta-4 (HSPB4) gene], which is located on chromosome 21q22.3 (Quax-Jeuken et al. 1985). The CRYAA gene consists of three coding exons that encode a 173-amino acid structural protein called alpha-crystallin that protects lens fiber cells from heat-induced necrosis, as well as facilitates in the maintenance of lens transparency. Animal studies using mouse models have shown that alpha-crystallins assist in the normal embryologic development of the anterior segment of the eye. Targeted disruption of the CRYAA gene results in the development of cataracts and the accumulation of cytoplasmic bodies consisting of alpha-B-cystallins. These findings suggest that the CRYAA protein interacts with the crystallin, alpha-b protein as a molecular chaperone to maintain protein solubility, which, when disrupted, results in lens opacity leading to the formation of cataracts (Brady et al. 1997; Graw et al. 2001; Fu and Liang 2002, 2003; Hsu et al. 2006). To date, a total of about 15 pathogenic CRYAA sequence variants have been reported. These variants are mostly missense, small in-frame deletions, and only a few chain termination (nonsense) variants (Human Gene Mutation Database). It has been hypothesized that the missense variants result in changes in charge dispersion at the surface of the CRYAA protein, which is critical for chaperone action and stability (Litt et al. 1998; Mackay et al. 2003; Graw et al. 2001; Vanita et al. 2006; Santhiya et al. 2006).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test may range up to 30%. In India, none of the 100 congenital cataract cases showed causative CRYAA sequence variants (Kumar et al. 2013). In Australia, 25% (1/4) families with autosomal dominant congenital cataract tested positive for disease-causing CRYAA sequence variants (Laurie et al. 2012). In Denmark, 30% (3/10) of families with hereditary congenital cataract harbored pathogenic sequence variants in the CRYAA gene (Hansen et al. 2007).

Testing Strategy

This test provides full coverage of all coding exons of the CRYAA 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 ideal CRYAA test candidates are individuals who present with congenital, autosomal dominant cataract.

Gene

Official Gene Symbol OMIM ID
CRYAA 123580
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Cataract 9 AD 604219

Related Test

Name
Congenital Cataracts Panel

Citations

  • American Academy of Pediatrics. 2002. Pediatrics. 109: 980-1. PubMed ID: 11986467
  • Beby F. et al. 2007. Archives of Ophthalmology (chicago, Ill. : 1960). 125: 213-6. PubMed ID: 17296897
  • Brady JP. et al. 1997. Proceedings of the National Academy of Sciences of the United States of America. 94: 884-9. PubMed ID: 9023351
  • Fu L., Liang JJ. 2002. The Journal of Biological Chemistry. 277: 4255-60. PubMed ID: 11700327
  • Fu L., Liang JJ. 2003. Investigative Ophthalmology & Visual Science. 44: 1155-9. PubMed ID: 12601044
  • Graw Jochen et al. 2001. Investigative Ophthalmology & Visual Science. 42: 2909–2915. PubMed ID: 11687536
  • Hansen L. et al. 2007. Investigative Ophthalmology & Visual Science. 48: 3937-44. PubMed ID: 17724170
  • Hejtmancik J.F. 2008. Seminars in cell & developmental biology. 19: 134-49. PubMed ID: 18035564
  • Hsu CD. et al. 2006. Investigative Ophthalmology & Visual Science. 47: 2036-44. PubMed ID: 16639013
  • Human Gene Mutation Database (Bio-base).
  • Javadiyan S. et al. 2016. Bmc Research Notes. 9: 83. PubMed ID: 26867756
  • Kumar M. et al. 2013. Molecular Vision. 19: 2436-50. PubMed ID: 24319337
  • Laurie KJ. et al. 2013. Human Mutation. 34: 435-8. PubMed ID: 23255486
  • Li LH. et al. 2013. The British Journal of Ophthalmology. 97: 588-91. PubMed ID: 23426739
  • Litt M. et al. 1998. Human Molecular Genetics. 7: 471-4. PubMed ID: 9467006
  • Mackay DS. et al. 2003. European Journal of Human Genetics : Ejhg. 11: 784-93. PubMed ID: 14512969
  • Quax-Jeuken Y. et al. 1985. Proceedings of the National Academy of Sciences of the United States of America. 82: 5819-23. PubMed ID: 3862098
  • Santhiya ST. et al. 2006. Molecular Vision. 12: 768-73. PubMed ID: 16862070
  • Shafie SM. et al. 2006. American Journal of Ophthalmology. 141: 750-2. PubMed ID: 16564818
  • Vanita V. et al. 2006. Molecular Vision. 12: 518-22. PubMed ID: 16735993
  • Ventura MC. et al. 2013. Arquivos Brasileiros De Oftalmologia. 76: 240-3. PubMed ID: 24061837
  • Wirth MG. et al. 2002. The British Journal of Ophthalmology. 86: 782-6. PubMed ID: 12084750
  • Yi J. et al. 2011. International Journal of Ophthalmology. 4: 422-32. PubMed ID: 22553694

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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