Deafness, Autosomal Dominant 44 (DFNA44) via the CCDC50 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
11151 CCDC50 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11151CCDC5081479 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

Hereditary or familial hearing loss (HL) and deafness can be prelingual (before language develops) or postlingual (after language develops) and may be conductive, sensorineural, or a combination of both. Causes for hereditary HL can be syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems). Familial forms of hearing loss must be distinguished from acquired (non-genetic) causes of hearing loss (such as environmental effects or mechanical stress) and are diagnosed by otologic, audiologic, and physical examination, family history, ancillary testing (e.g., CT examination of the temporal bone), and molecular genetic testing. Molecular genetic testing is possible for many types of syndromic and nonsyndromic deafness and plays a prominent role in diagnosis and genetic counseling (Smith et al. 2013).

Nonsyndromic hearing loss and deafness is characterized by childhood-onset, progressive, moderate-to-severe sensorineural hearing impairment. The audioprofile may vary significantly, even among family members. Affected individuals have no other associated medical findings (Smith et al. 2013).

DFNA44 was found in a Spanish family segregating for progressive, postlingual, nonsyndromic sensorineural hearing loss. Initial hearing loss is moderate and affects mainly low to mid frequencies, progressing to involve all frequencies. Onset is typically 6-10 years of age with profound hearing loss by the 6th decade (Modamio-Hoybjor et al. 2007).

Genetics

The different gene loci for nonsyndromic hearing loss are designated DFN (for DeaFNess) and named on the mode of inheritance; DFNA for autosomal dominant, DFNB for autosomal recessive and DFNX for X-linked inheritance respectively. Nonsyndromic hearing loss and deafness via CCDC50 exhibits an autosomal dominant mode of inheritance corresponding to DFNA44.

The only documented DFNA44 causative variant is an 8 bp duplication (c.1394_1401dupCACGGCAT) in exon 11 of CCDC50. This variant results in a frameshift (p.Phe468Hisfs*37) replacing the last 15 aa of the CCDC50 protein with a novel 36 aa sequence (Modamio-Hoybjor et al. 2007).

The CCDC50 (coiled-coil domain containing 50) gene codes for the protein Ymer, a soluble, cytoplasmic, tyrosine-phosphorylated protein with multiple ubiquitin-interacting domains that is expressed in many different tissues (Tashiro et al. 2006; Modamio-Hoybjor et al. 2007). Ymer is involved with inhibition of EGF receptor down-regulation and regulation of NF-kB signaling (Tashiro et al. 2006; Tsukiyama et al. 2012). In the mouse inner ear Ymer is expressed in cochlear mesenchyme structures and nerve fibers during embryonic stages, as well as pillar cells, outer hair cells, Deiter’s cells and the stria vascularis during adult stages. Ymer colocalizes with microtubules of the cytoskeleton in the mouse inner ear, important structures for proper function of pillar cells and the stria vascularis. Destabilization of the cytoskeleton in these components of the inner ear over time may explain progressive hearing loss features of DFNA44 (Modamio-Hoybjor et al. 2007).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be estimated because only one pathogenic variant has been documented in a single Spanish family.

Testing Strategy

This test provides full coverage of all coding exons of the CCDC50 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) postlingual, mild to profound, progressive sensorineural hearing impairment, 2) no related systemic findings identified by medical history and physical examination and/or 3) a family history of nonsyndromic hearing loss consistent with autosomal dominant inheritance.

Gene

Official Gene Symbol OMIM ID
CCDC50 611051
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Dominant 44 AD 607453

Citations

  • Modamio-Hoybjor S. et al. 2007. American Journal of Human Genetics. 80: 1076-89. PubMed ID: 17503326
  • Smith R.J.H. et al. 2013. Deafness and Hereditary Hearing Loss Overview. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301607
  • Tashiro K. et al. 2006. The Journal of Biological Chemistry. 281: 24612-22. PubMed ID: 16803894
  • Tsukiyama T. et al. 2012. Molecular Medicine (cambridge, Mass.). 18: 587-97. PubMed ID: 22331027

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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