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Deafness, Autosomal Dominant 40 (DFNA40) via the CRYM 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
3995 CRYM 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3995CRYM81479 81479,81479 $990 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 platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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 CRYM gene is associated with pre- or postlingual, bilateral, moderate to severe, nonprogressive or progressive sensorineural hearing impairment affecting all frequencies. No visual, vestibular or temporal bone abnormalities are present (Abe et al. 2003).

Genetics

DFNA40 is an autosomal dominant hearing disorder that is caused by pathogenic sequence variants in the crystallin mu (CRYM) gene, which is located on chromosome 16p12.2. The CRYM gene spans 48.6 kb and consists of 8 coding exons that produce a 314 amino acid protein that is expressed in human inner ear, retina, heart, brain, muscle and kidney (Abe et al. 2003; Kim et al. 1992). In the mouse inner ear the CRYM gene is expressed in fibrocytes of the lateral wall of the cochlea, but not in the inner or outer hair cells (Abe et al. 2003; Oshima et al. 2006).

Only one missense and one nonsense variant in CRYM have been reported to date as pathogenic for hearing loss in two different families of Japanese origin (Abe et al. 2003).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this sequencing test is difficult to predict because only one missense and one nonsense variant in CRYM have been reported as pathogenic for hearing loss in two different families of Japanese origin (Abe et al. 2003). Analytical sensitivity should be high because all reported variants are detectable by sequencing.

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

Testing Strategy

This test provides full coverage of all coding exons of the CRYM 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 CRYM gene is suspected in individuals with the following: pre- or postlingual, bilateral, moderate to severe, nonprogressive or progressive sensorineural hearing impairment affecting all frequencies; no related systemic findings identified by medical history and physical examination; or a family history of nonsyndromic hearing loss consistent with autosomal dominant inheritance.

Gene

Official Gene Symbol OMIM ID
CRYM 123740
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Dominant 40 AD 616357

Citations

  • Abe S. et al. 2003. American Journal of Human Genetics. 72: 73-82. PubMed ID: 12471561
  • Ciuman R.R. 2013. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 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
  • Kim R.Y. et al. 1992. Proceedings of the National Academy of Sciences of the United States of America. 89: 9292-6. PubMed ID: 1384048
  • Oshima A. et al. 2006. Journal of Medical Genetics. 43: e25. PubMed ID: 16740909
  • 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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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View Ordering Instructions

1) Select Test Method (Platform)


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.
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