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Deafness, Autosomal Recessive 25 (DFNB25) via the GRXCR1 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
4005 GRXCR1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4005GRXCR181479 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

Nonsyndromic hearing loss is characterized by difficulty or inability to hear that is not associated with any visible defects involving the external ear, other organs, or any other medical condition. Nonsyndromic hearing loss may be associated with abnormalities involving the middle ear and/or the inner ear (Ciuman 2013; Dodson et al. 2011; Hilgert et al. 2009). At least 70% of cases involving hearing loss are nonsyndromic (Van Camp et al. 1997).

Nonsyndromic hearing loss and deafness due to pathogenic variants in the GRXCR1 gene is associated with congenital or early-onset, bilateral, moderate to profound, progressive sensorineural hearing impairment. Vestibular dysfunction is present in some patients with a childhood onset (Schraders et al. 2010).

Genetics

DFNB25 is an autosomal recessive hearing disorder that is caused by pathogenic sequence variants in the glutaredoxin and cysteine rich domain containing 1 (GRXCR1) gene, which is located on chromosome 4p13. The GRXCR1 gene spans 141 kb and consists of 4 coding exons that produce a 290 amino acid protein. Two missense, four nonsense and two splicing variants in the GRXCR1 gene in the homozygous or compound heterozygous state have been reported as pathogenic for hearing loss in families of Dutch, Pakistani, Turkish and Japanese ancestry (Schraders et al. 2010; Odeh et al. 2010; Mori et al. 2015; Bademci et al. 2016; Sloan-Heggen et al. 2016). The GRXCR1 gene is expressed in the sensory epithelia of the inner ear of the mouse and the GRXCR1 protein is localized to the stereocilia of vestibular hair cells (Odeh et al. 2010).

Clinical Sensitivity - Sequencing with CNV PGxome

In a study of 1,119 patients with hearing loss in which 440 patients received a genetic diagnosis, only one pathogenic variant in GRXCR1 was detected (Sloan-Heggen et al. 2016). Only two missense, four nonsense and two splicing variants in GRXCR1 have been reported as pathogenic for hearing loss (Schraders et al. 2010; Odeh et al. 2010; Mori et al. 2015; Bademci et al. 2016; Sloan-Heggen et al. 2016). Analytical sensitivity should be high because all reported variants are detectable by sequencing.

No deletion or duplication variants associated with GRXCR1 have been reported as pathogenic for hearing loss.

Testing Strategy

This test provides full coverage of all coding exons of the GRXCR1 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

Nonsyndromic hearing loss and deafness due to variants in the GRXCR1 gene is suspected in individuals with the following: congenital or early-onset, bilateral, moderate to profound, progressive sensorineural hearing impairment; with or without vestibular dysfunction; no other related systemic findings identified by medical history and physical examination; and/or a family history of nonsyndromic hearing loss consistent with autosomal recessive inheritance. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GRXCR1.

Gene

Official Gene Symbol OMIM ID
GRXCR1 613283
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Recessive 25 AR 613285

Citations

  • Bademci G. et al. 2016. Genetics in Medicine. 18: 364-71. PubMed ID: 26226137
  • Ciuman R.R. 2013. Medical Science Monitor . 19: 1195-210. PubMed ID: 24362017
  • Dodson K.M. et al. 2011. American Journal of Medical Genetics. Part A. 155A: 993-1000. PubMed ID: 21465647
  • Hilgert N. et al. 2009. Mutation Research. 681: 189-96. PubMed ID: 18804553
  • Mori K. et al. 2015. The Annals of Otology, Rhinology, and Laryngology. 124 Suppl 1: 129S-34S. PubMed ID: 25802247
  • Odeh H. et al. 2010. American Journal of Human Genetics. 86: 148-60. PubMed ID: 20137774
  • Schraders M. et al. 2010. American Journal of Human Genetics. 86: 138-47. PubMed ID: 20137778
  • Sloan-Heggen C.M. et al. 2016. Human Genetics. 135: 441-50. PubMed ID: 26969326
  • Van Camp G. et al. 1997. American Journal of Human Genetics. 60: 758-64. PubMed ID: 9106521

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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