Deafness, Autosomal Recessive 49 (DFNB49) via the MARVELD2 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
4053 MARVELD2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4053MARVELD281479 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

Autosomal recessive deafness 49 (DFNB49) is characterized by prelingual, bilateral, moderate to profound, stable, all-frequency, symmetrical, sensorineural nonsyndromic hearing loss (Chisti et al. 2008). 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 DFNB49 individuals is usually flat, indicating hearing loss at all frequencies (Ramzan et al. 2008; Chisti et al. 2008). Individuals diagnosed with DFNB49 generally do not present with features of visual loss, deformities involving the limbs, mental deficiency, or disruption of vestabular organization.

Genetics

DFNB49 is an autosomal recessive hearing disorder that is caused by pathogenic sequence variants in the marvel domain-containing protein 2 (MARVELD2) gene, which is located on chromosome 5q13.2 (Ramzan et al. 2005). The MARVELD2 gene consists of 6 coding exons that encode a 558-amino acid membrane protein known as tricellulin, which plays a major role in the regulation of movement of solutes across cells and tissues (Ikenouchi et al. 2005; Riazuddin et al. 2006; Higashi et. al. 2013). In the epithelial cells of the inner ear, tricellulin is expressed in the tricellular tight junctions, which are regions within the organ of Corti that contain potassium ion (K+)-rich endolymphatic fluid that is required for the conduction of sound (Kitajiri et al. 2004). The presence of tricellulin in the inner ear epithelial cells ensures tightness in these cellular junctions, which is essential for hearing (Chisti et al. 2008). Previous studies have suggested that deafness is caused by an increase in either the concentration of K+ ions or small molecules such as adenosine triphosphate (ATP) around the hair bundle, which results in an abnormal endocochlear potential, ultimately resulting in hair cell dysfunction and degeneration (Mariano et al. 2011; Higashi et al. 2013). Gene knockout studies using a mouse model showed early-onset hearing loss that was associated with the degeneration of inner ear hair cells (Nayak et al. 2013; Kamitani et al. 2015). To date, a total of about 13 pathogenic MARVELD2 sequence variants have been reported, which include 5 missense/nonsense, 4 splicing, 3 small deletions, and 1 gross deletion (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test has been reported to range from 0.1% to 11.8%. Causative variants in the MARVELD2 gene were detected in 0.6% (1/160) of families with autosomal recessive nonsyndromic hearing loss (Bademci et al. 2015). In Iran, 0.7% (1/144) of families with autosomal recessive nonsyndromic hearing loss harbored pathogenic MARVELD2 sequence variants (Babanejad et al. 2012). Around 1% (3/284) of Pakistani families diagnosed with autosomal recessive nonsyndromic hearing loss harbored causative sequence variants in the MARVELD2 gene (Chisti et al. 2008). In two independent research studies conducted in Japan, around 0.1% (1/1,20; Nishio and Usami 2015) and 1.9% (4/216; Miyagawa et al. 2013) of deaf patients tested positive for pathogenic MARVELD2 sequence variants. In Turkey, pathogenic sequence variants in the MARVELD2 gene were detected in 3.4% (1/29) of families with autosomal recessive nonsyndromic hearing loss (Atik et al. 2015). Diseasing-causing MARVELD2 sequence variants were observed in 4.2% (6/143) of deaf Slovakian families who tested negative for GJB2 pathogenic sequence variants and 11.8% (10/85) of Hungarian patients with hearing impairment (Masindova et al. 2015).

Testing Strategy

This test provides full coverage of all coding exons of the MARVELD2 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 MARVELD2 test candidates are individuals who present with prelingual, bilateral, moderate to profound, stable, all-frequency, symmetrical, autosomal recessive nonsyndromic hearing loss. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in MARVELD2.

Gene

Official Gene Symbol OMIM ID
MARVELD2 610572
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Recessive 49 AR 610153

Citations

  • Atik T. et al. 2015. Plos One. 10: e0142154. PubMed ID: 26561413
  • Babanejad M. et al. 2012. American Journal of Medical Genetics. Part A. 158A: 2485-92. PubMed ID: 22903915
  • Bademci G. et al. 2015. Genetics in Medicine : Official Journal of the American College of Medical Genetics. 0: N/A. PubMed ID: 26226137
  • Chishti M.S. et al. 2008. Journal of Human Genetics. 53: 101-5. PubMed ID: 18084694
  • Higashi T. et al. 2013. The Journal of Clinical Investigation. 123: 3712-5. PubMed ID: 23979155
  • Hildebrand M.S. et al. 2008. Genetics in Medicine. 10: 797-804. PubMed ID: 18941426
  • Human Gene Mutation Database (Bio-base).
  • Ikenouchi J. et al. 2005. The Journal of Cell Biology. 171: 939-45. PubMed ID: 16365161
  • Kamitani T. et al. 2015. Scientific Reports. 5: 18402. PubMed ID: 26677943
  • Kitajiri S. et al. 2004. Journal of Cell Science. 117: 5087-96. PubMed ID: 15456848
  • Mariano C. et al. 2011. European Journal of Cell Biology. 90: 787-96. PubMed ID: 21868126
  • Mašindová I. et al. 2015. Plos One. 10: e0124232. PubMed ID: 25885414
  • Miyagawa M. et al. 2013. PLoS One. 8: e71381. PubMed ID: 23967202
  • Nayak G. et al. 2013. The Journal of Clinical Investigation. 123: 4036-49. PubMed ID: 23979167
  • Nishio SY., Usami S. 2015. The Annals of Otology, Rhinology, and Laryngology. 124 Suppl 1: 49S-60S. PubMed ID: 25788563
  • Ramzan K. et al. 2005. Human Genetics. 116: 17-22. PubMed ID: 15538632
  • Riazuddin S. et al. 2006. American Journal of Human Genetics. 79: 1040-51. PubMed ID: 17186462

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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