Cataract 3, Multiple Types (CTRCT3) via the CRYBB2 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
3887 CRYBB2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3887CRYBB281479 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

  • Jamie Fox, PhD

Clinical Features and Genetics

Clinical Features

Cataract 3 (CTRCT3) is common congenital, bilateral, symmetrical, progressive, polymorphic vision disorder that causes blindness in children (Litt et al. 1997). It consists of multiple types of cataracts that have been described as structural cataracts with punctate and cerulean (peripheral bluish and white opacification in concentric layers) opacities (Pauli et al. 2007). CTRCT3 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 1998). Intrafamilial variability in the size and density of the sutural opacity or in the number and position of the cerulean spots commonly occurs in CTRCT3 (Vanita et al. 2001; Lou et al. 2009; Weisschuh et al. 2012). The majority of individuals with CTRCT3 notice visual impairment before the age of 10 (Kramer et al. 1996; Li et al. 2008; Mothobi et al. 2009). 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 (Yao et al. 2005, 2011; 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). Some individuals with CTRCT3 may exhibit microphthalmia, microcornea, and strabismus (Kramer et al. 1996).

Genetics

CTRCT3 is an autosomal dominant vision disorder that is caused by pathogenic sequence variants in the crystallin, beta-B2 (CRYBB2) gene, which is located on chromosome 22q11.23 (Kramer et al. 1996; Garnai et al. 2014). The CRYBB2 gene consists of five coding exons that encode a 205-amino acid structural protein called beta-crystallin B2, which is the most abundant and water-soluble beta-crystallin protein in the epithelial cells of the human lens (Gill et al. 2000). The CRYBB2 protein plays an important structural role in the maintenance of lens transparency and refractive index (Chen et al. 2013). Pathogenic sequence variants in the CRYBB2 gene significantly reduces the solubility and changes biophysical properties of the beta-crystallin B2, which are critical for lens transparency (Liu and Liang 2005; Chen et al. 2013). To date, a total of about 20 pathogenic CRYBB2 sequence variants have been reported, which are mostly missense and a few chain terminations (nonsense) and complex rearrangements (Human Gene Mutation Database). A recent study has indicated that the CRYBB2 protein is also expressed in the mammalian brain and may play a role in hippocampal function and behavioral phenotypes (Sun et al. 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test may range up to 10%. In three independent investigations performed in China, none (0/25; Sun et al. 2011), 5.6% (1/18; Sun et al. 2014), and 10% (2/20; Wang et al. 2011) of families with congenital cataracts harbored pathogenic sequence variants in the CRYBB2 gene. In two independent studies conducted in India, 1.7% (1/60; Devi et al. 2008), 2% (2/100; Kumar et al. 2013) of families with inherited pediatric cataract tested positive for disease-causing CRYBB2 sequence variants. In Denmark, 7% (2/28) of families with hereditary congenital cataract carried a pathogenic sequence variant in the CRYBB2 gene (Hansen et al. 2009).

Testing Strategy

This test provides full coverage of all coding exons of the CRYBB2 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 CRYBB2 test candidates are individuals who present with congenital cataracts.

Gene

Official Gene Symbol OMIM ID
CRYBB2 123620
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Cataract 3 AD 601547

Citations

  • American Academy of Pediatrics. 2002. Pediatrics. 109: 980-1. PubMed ID: 11986467
  • Chen W. et al. 2013. Plos One. 8: e81290. PubMed ID: 24312286
  • Devi R.R. et al. 2008. Molecular Vision. 14: 1157-70. PubMed ID: 18587492
  • Garnai S.J. et al. 2014. Molecular Vision. 20: 1579-93. PubMed ID: 25489230
  • Gill D. et al. 2000. Investigative Ophthalmology & Visual Science. 41: 159-65. PubMed ID: 10634616
  • Hansen L. et al. 2009. Investigative Ophthalmology & Visual Science. 50: 3291-303. PubMed ID: 19182255
  • Hejtmancik J.F. 1998. American Journal of Human Genetics. 62: 520-5. PubMed ID: 9497271
  • Human Gene Mutation Database (Bio-base).
  • Kramer P. et al. 1996. Genomics. 35: 539-42. PubMed ID: 8812489
  • Kumar M. et al. 2013. Molecular Vision. 19: 2436-50. PubMed ID: 24319337
  • Li Fei-feng et al. 2008. Molecular Vision. 14: N/A. PubMed ID: 18449377
  • Li L.H. et al. 2013. The British Journal of Ophthalmology. 97: 588-91. PubMed ID: 23426739
  • Litt M. et al. 1997. Human Molecular Genetics. 6: 665-8. PubMed ID: 9158139
  • Liu B.F., Liang J.J. 2005. Molecular Vision. 11: 321-7. PubMed ID: 15889016
  • Lou D. et al. 2009. Eye (London, England). 23: 1213-20. PubMed ID: 18617901
  • Mothobi M.E. et al. 2009. Molecular Vision. 15: 1470-5. PubMed ID: 19649175
  • Pauli S. et al. 2007. Molecular Vision. 13: 962-7. PubMed ID: 17653036
  • Sun M. et al. 2013. Mammalian Genome. 24: 333-48. PubMed ID: 24096375
  • Sun W. et al. 2011. Molecular vision. 17: 2197-206. PubMed ID: 21866213
  • Sun W. et al. 2014. Plos One. 9: e100455. PubMed ID: 24968223
  • Vanita V. et al. 2001. J. Med. Genet. 38: 396-400. PubMed ID: 11424921
  • Ventura M.C. et al. 2013. Arquivos Brasileiros De Oftalmologia. 76: 240-3. PubMed ID: 24061837
  • Wang K.J. et al. 2011. Archives of Ophthalmology (Chicago, Ill.: 1960). 129: 337-43. PubMed ID: 21402992
  • Weisschuh N. et al. 2012. Molecular Vision. 18: 174-80. PubMed ID: 22312185
  • Wirth M.G. et al. 2002. The British Journal of Ophthalmology. 86: 782-6. PubMed ID: 12084750
  • Yao K. et al. 2005. Molecular Vision. 11: 758-63. PubMed ID: 16179907
  • Yao K. et al. 2011. Molecular Vision. 17: 144-52. PubMed ID: 21245961
  • 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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