Usher Syndrome Type 2C and Deafness, Autosomal Recessive 57 (DFNB57) via the PDZD7 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
11567 PDZD7 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11567PDZD781479 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. 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

  • Ben Dorshorst, PhD

Clinical Features and Genetics

Clinical Features

Usher syndrome is a clinically heterogeneous disorder characterized by progressive retinitis pigmentosa (RP) and sensorineural hearing impairment, with or without vestibular abnormalities. Three types are recognized based on the age of onset, severity of symptoms, and the vestibular involvement (Smith et al. 1994). Usher syndrome type 2 (USH2) is characterized by mild to severe congenital hearing loss, RP with onset in the teens, and normal vestibular function. Features of RP include night blindness progressing to constriction of the peripheral visual field with eventually loss of central vision, abnormal fundus with bone-spicule deposits/attenuated retinal vessels, and abnormal electroretinographic (ERG) findings (Daiger et al. 2007). USH2C audiograms are slightly downsloping and show a moderate to severe hearing loss across all frequencies (Hilgert et al. 2009).

Genetics

Usher syndrome type 2 (USH2) is a genetically heterogeneous autosomal recessive disease. Variants in three genes: USH2A, GPR98 (ADGRV1), and DFNB31 account for nearly all cases with detectable variants (Eudy et al. 1998; Weston et al. 2004; Mburu et al. 2003; Keats and Lentz 2010). PDZD7 is a homolog of genes causing USH1C and USH2D and encodes a binding protein that is expressed in the mechanosensory hair cells of the inner ear (Ebermann et al. 2010, Zou et al. 2014). Digenic inheritance of USH2C was reported in a single German individual with heterozygous frameshift variants in both GPR98 and PDZD7 (Ebermann et al. 2010). A different frameshift variant in PDZD7 was shown to increase the severity of retinal disease in patients with USH2A variants (Ebermann et al. 2010). PDZD7 was shown to interact with the Usher proteins GPR98 and USH2A in yeast-2-hybrid and coimmunoprecipitation studies, supporting the model of digenic inheritance of USH2C via variants in GPR98 and PDZD7 as well as the retinal disease modifying effect of variants in PDZD7 on patients with USH2A (Ebermann et al. 2010). Homozygosity for a balanced reciprocal translocation between the long arms of chromosomes 10 and 11 that disrupts PDZD7 transcripts was found to cause congenital bilateral moderate sensorineural hearing loss in a four year old boy. No RP or vestibular dysfunction was observed over the next five years, although development of RP later in life cannot be ruled out (Schneider et al. 2009).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be estimated because PDZD7 pathogenic variants have been documented in only a small number of patients with Usher syndrome or autosomal recessive nonsyndromic hearing loss.

Testing Strategy

This test provides full coverage of all coding exons of the PDZD7 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 1) combined congenital sensorineural hearing loss, RP and normal vestibular function consistent with autosomal recessive inheritance, 2) nonsyndromic hearing loss consistent with autosomal recessive inheritance or 3) heterozygous USH2A or GPR98 variants or those with homozygous variants in either USH2A or GPR98 and unusually severe symptoms. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PDZD7.

Gene

Official Gene Symbol OMIM ID
PDZD7 612971
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Usher Syndrome, Type 2C AR 605472

Citations

  • Daiger S.P. et al. 2007. Archives of Ophthalmology (chicago, Ill. : 1960). 125: 151-8. PubMed ID: 17296890
  • Ebermann I. et al. 2010. The Journal of Clinical Investigation. 120: 1812-23. PubMed ID: 20440071
  • Eudy J.D. et al. 1998. Science (new York, N.y.). 280: 1753-7. PubMed ID: 9624053
  • Hilgert N. et al. 2009. Journal of Medical Genetics. 46: 272-6. PubMed ID: 19357116 PubMed ID: 19357116
  • Keats BJ, Lentz J. 2010. Usher Syndrome Type I. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301442
  • Mburu P. et al. 2003. Nature Genetics. 34: 421-8. PubMed ID: 12833159
  • Schneider E. et al. 2009. Human Molecular Genetics. 18: 655-66. PubMed ID: 19028668
  • Smith R.J.H. et al. 1994. American Journal of Medical Genetics. 50: 32-8. PubMed ID: 8160750
  • Weston M.D. et al. 2004. American Journal of Human Genetics. 74: 357-66. PubMed ID: 14740321
  • Zou et al. 2014. PubMed ID: 24334608

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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