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Deafness, Autosomal Recessive 63 (DFNB63) via the LRTOMT 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
4011 LRTOMT 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4011LRTOMT81479 81479,81479 $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

Deafness, autosomal recessive 63 (DFNB63) is a prelingual, bilateral, nonprogressive, nonsyndromic, sensorineural hearing loss disorder with variable frequency impairment, wherein some may show impairment to all frequencies, whereas others only involve mid- to high frequencies (Tlili et al. 2007). 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 audiograms of DFNA63 individuals generally show gently downward-sloping to flat pure tone audiograms, indicating mid-/high-frequency to all-frequency hearing impairment (Ichinose et al. 2015). DFNB63 patients show no signs of vestibular dysfunction or skin, renal, or optic anomalies.

Genetics

DFNA63 is an autosomal recessive hearing disorder that is caused by pathogenic sequence variants in the leucine-rich transmembrane O-methyltransferase (LRTOMT) gene (previously called leucine-rich repeat-containing protein 51 (LRRC51), which is located on chromosome 11q13.4 (Ahmed et al. 2008). The LRTOMT gene consists of 10 coding exons and generates two alternative reading frames, thus encoding two different proteins, namely LRTOMT1 and LRTOMT2, which differ by their translation start codons. LRTOMT1 is encoded when translation starts in exon 3, and has a predicted transmembrane domain and two leucine-rich repeats. LRTOMT2 is encoded when translation begins in exon 5, and is predicted to comprise a catechol-O-methyltransferase domain (Ahmed et al. 2008). The LRTOMT1 protein is most prominently expressed along the basolateral wall of outer hair cells and distributed throughout the cytoplasm, thereby providing structural support (Ahmed et al. 2008). The LRTOMT2 protein is also highly expressed in sensory hair cells of the inner ear and is essential for auditory and vestibular function (Du et al. 2008). To date, a total of about 15 pathogenic LRTOMT sequence variants have been reported, all of which exclusively affect the LRTOMT2 protein. These include 10 missense and 2 protein truncating sequence variants, 1 splicing variant and 2 small deletions (Vanwesemael et al. 2011; Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test has been reported to range up to 2%. For example, in Iran, 0.7% (1/144) of families with autosomal recessive nonsyndromic hearing loss carried disease-causing sequence variants in the LRTOMT gene (Babanejad et al. 2012). In Japan, 0.9% (1/106) patients with sensorineural hearing loss from nonconsanguineous families showed causative LRTOMT sequence variants (Ichinose et al. 2015). In Turkey, 2% (1/49) of consanguineous families with nonsyndromic hearing loss tested positive for causative variants in the LRTOMT gene (Duman et al. 2011).

Testing Strategy

This test provides full coverage of all coding exons of the LRTOMT 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 LRTOMT test candidates are individuals who present with prelingual, bilateral, nonprogressive, sensorineural, autosomal recessive nonsyndromic hearing loss. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LRTOMT.

Gene

Official Gene Symbol OMIM ID
LRTOMT 612414
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Recessive 63 AR 611451

Citations

  • Ahmed Z.M. et al. 2008. Nature Genetics. 40: 1335-40. PubMed ID: 18953341
  • Babanejad M. et al. 2012. American Journal of Medical Genetics. Part A. 158A: 2485-92. PubMed ID: 22903915
  • Du X. et al. 2008. Proceedings of the National Academy of Sciences of the United States of America. 105: 14609-14. PubMed ID: 18794526
  • Duman D. et al. 2011. Genetic Testing and Molecular Biomarkers. 15: 29-33. PubMed ID: 21117948
  • Hildebrand M.S. et al. 2008. Genetics in Medicine. 10: 797-804. PubMed ID: 18941426
  • Human Gene Mutation Database (Bio-base).
  • Ichinose A. et al. 2015. The Annals of Otology, Rhinology, and Laryngology. 124 Suppl 1: 142S-7S. PubMed ID: 25788562
  • Tlili A. et al. 2007. Annals of Human Genetics. 71: 271-5. PubMed ID: 17166180
  • Vanwesemael M. et al. 2011. American Journal of Medical Genetics. Part A. 155A: 2021-3. PubMed ID: 21739586

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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