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Deafness, Autosomal Recessive 29 (DFNB29) via the CLDN14 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
3993 CLDN14 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3993CLDN1481479 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

Autosomal recessive deafness 29 (DFNB29) is characterized by prelingual, bilateral, severe to profound, nonprogressive, sensorineural nonsyndromic hearing loss affecting all frequencies, with more severe impairment at high frequencies (Bashir et al. 2010, Bashir et al. 2013). The audioprofile of most nonsyndromic hearing loss cases can be distinct, thus assisting in the development of an evaluation strategy for molecular genetic testing and in generating a prognosis on the rate of hearing loss per year (Hildebrand et al. 2008). Pure-tone audiometry of DFNB29 individuals generally show a downward sloping audiogram (Lee et al. 2012).

Genetics

DFNB29 is an autosomal recessive hearing disorder that is caused by pathogenic sequence variants in the claudin 14 (CLDN14) gene, which is located on chromosome 21q22.13n (Hattori et al. 2000). The CLDN14 gene consists of one coding exon that encodes a 239-amino acid protein that constitutes the fibrils of tight junctions and mainly functions in selective paracellular permeability (Wattenhofer et al. 2005). The claudin-14 protein is mainly expressed in the inner ear and plays a major role in decreasing cellular permeability to cations, particularly potassium. Claudin-14 is also expressed in the liver and kidney (Ben-Yosef et al. 2003). Pathogenic sequence variants in the CLDN14 gene result in impairment of the ability to form tight junctions, which is crucial for maintenance of an eletrochemical gradient between the endolymph and the surrounding tissues of the inner ear for proper hearing (Wilcox et al. 2001; Chiba et al. 2008). Gene knockout studies using mouse models have shown that deletion of the CLDN14 gene results in the rapid degeneration of the outer hair cells of the cochlea (Ben-Yosef et al. 2003). To date, a total of about 8 pathogenic CLDN14 sequence variants have been reported, which include 6 missense, 1 frame shift, and 1 truncation sequence variant that generates a non-functional claudin-14 protein (Lee et al. 2012; Human Gene Mutation Database). The CLDN14 gene has also been associated with susceptibility to kidney stones (Thorleifsson et al. 2009).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test has been reported to range from 2% to 3%. For example, in two separate studies conducted in Pakistan, 1.9% (15/800) of families with hearing loss (Bashir et al. 2013) and 2.2% (2/88) of families with moderately severe to severe hearing loss (Bashir et al. 2010) showed disease-causing CLDN14 sequence variants. In Iran, 2.8% (4/144) of families with autosomal recessive nonsyndromic hearing loss that tested negative for pathogenic variants in the GJB2 gene showed disease-causing variants in the CLDN14 gene (Babanejad et al. 2012).

Testing Strategy

This test provides full coverage of all coding exons of the CLDN14 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

The ideal CLDN14 test candidates are individuals who present with prelingual, bilateral, severe to profound, nonprogressive, sensorineural, autosomal recessive nonsyndromic hearing loss that affects all frequencies, with more severe impairment at high frequencies. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CLDN14.

Gene

Official Gene Symbol OMIM ID
CLDN14 605608
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Recessive 29 AR 614035

Citations

  • Babanejad M. et al. 2012. American Journal of Medical Genetics. Part A. 158A: 2485-92. PubMed ID: 22903915
  • Bashir R. et al. 2010. Journal of Human Genetics. 55: 767-70. PubMed ID: 20811388
  • Bashir Z.E. et al. 2013. Journal of Human Genetics. 58: 102-8. PubMed ID: 23235333
  • Ben-Yosef T. et al. 2003. Human Molecular Genetics. 12: 2049-61. PubMed ID: 12913076
  • Chiba H. et al. 2008. Biochimica Et Biophysica Acta. 1778: 588-600. PubMed ID: 17916321
  • Hattori M. et al. 2000. Nature. 405: 311-9. PubMed ID: 10830953
  • Hildebrand M.S. et al. 2008. Genetics in Medicine. 10: 797-804. PubMed ID: 18941426
  • Human Gene Mutation Database (Bio-base).
  • Lee K. et al. 2012. American Journal of Medical Genetics. Part A. 158A: 315-21. PubMed ID: 22246673
  • Thorleifsson G. et al. 2009. Nature Genetics. 41: 926-30. PubMed ID: 19561606
  • Wattenhofer M. et al. 2005. Human Mutation. 25: 543-9. PubMed ID: 15880785
  • Wilcox E.R. et al. 2001. Cell. 104: 165-72. PubMed ID: 11163249

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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