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Sorsby Fundus Dystrophy via the TIMP3 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
9047 TIMP3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9047TIMP381479 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. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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

Sorsby fundus dystrophy, also called hemorrhagic macular dystrophy (SFD), is a rare maculopathy. The hallmark of SFD is a sudden reduction in visual acuity presenting in middle age, usually between the third and fifth decades in life. Additional symptoms include night blindness, prolongation of dark adaptation, and color vision deficiency. Clinical findings consist of drusen-like deposits at the level of Bruch’s membrane, subretinal deposits of yellow material, angioid streaks, and exudative lesions of the macula (Sorsby and Mason 1949; Jacobson et al. 1995). Optical coherence tomography (OCT) findings include hyperreflectivity of the retinal pigment epithelium-photoreceptor-choroid complex (Saihan et al. 2009). As the disease progresses, subretinal neovascularization and atrophy of the retinal pigment epithelium may also occur. This results in rapid bilateral loss of central vision in mid age and ultimately loss of peripheral vision later in life. Although rare, SFD has been reported in patients from various populations.

Genetics

Sorsby Fundus Dystrophy (SFD) is inherited in an autosomal dominant manner with age-dependent penetrance (Felbor et al. 1997). It is caused by heterozygous pathogenic variants in the TIMP3 gene (Weber et al. 1994). Over 15 pathogenic variants have been reported to date. Only two are truncating variants and the rest are missense (Human Gene Mutation Database). The TIMP3 gene encodes the tissue inhibitor of the metalloproteinase-3 protein, which is secreted by the retinal pigment epithelium (RPE) and incorporated into Bruch’s membrane (Della et al. 1996). Accumulation of TIMP3 has been reported in eyes of patients affected with SFD (Fariss et al. 1998).

Clinical Sensitivity - Sequencing with CNV PGxome

A study by Ayyagari et al. (2000) detected causative variants in TIMP3 in all Sorsby's fundus dystrophy (SFD) affected patients. However, a 4-generation pedigree with several affected family members with SFD-like phenotype did not have causative variants in TIMP3 (Ayyagari et al. 2000).

No large deletions or duplications in TIMP3 have been reported to date (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the TIMP3 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

Patients with a rapid decline of central vision during 4th or 5th decade and lose ambulatory vision 3-4 decades later are candidates.

Gene

Official Gene Symbol OMIM ID
TIMP3 188826
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Sorsby Fondus Dystrophy AD 136900

Citations

  • Ayyagari R. et al. 2000. Archives of Ophthalmology (chicago, Ill. : 1960). 118: 85-92. PubMed ID: 10636420
  • Della N.G. et al. 1996. Investigative Ophthalmology & Visual Science. 37: 1921-4. PubMed ID: 8759363
  • Fariss R.N. et al. 1998. The British Journal of Ophthalmology. 82: 1329-34. PubMed ID: 9924344
  • Felbor U. et al. 1997. American Journal of Human Genetics. 60: 57-62. PubMed ID: 8981947
  • Human Gene Mutation Database (Bio-base).
  • Jacobson S.G. et al. 1995. Nature Genetics. 11: 27-32. PubMed ID: 7550309
  • Saihan Z. et al. 2009. Molecular Vision. 15: 1218-30. PubMed ID: 19536307
  • Sorsby A. and Mason M.E. 1949. The British Journal of Ophthalmology. 33:67-97. PubMed ID: 18111349
  • Weber B.H. et al. 1994. Nature Genetics. 8: 352-6. PubMed ID: 7894485

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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