DNA icon

Deafness, Autosomal Recessive 67 (DFNB67) via the LHFPL5 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
4009 LHFPL5 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4009LHFPL581479 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 67 (DFNB67) is characterized by prelingual, bilateral, severe to profound, stable, sensorineural nonsyndromic hearing loss but without vestibular abnormalities (Kalay et al. 2006). Most DFNB67 individuals are born to consanguineous parents (Kalay et al. 2006).

Genetics

DFNB67 is an autosomal recessive hearing disorder that is caused by pathogenic sequence variants in the lipoma HMGIC fusion partner-like 5 (LHFPL5) gene, also known as the tetraspan membrane protein of hair cell sterocilia (TMHS) gene, which is located on chromosome 6p21.31 (Shabbir et al. 2006). The LHFPL5 gene consists of three coding exons that produce a 219-amino acid protein, which consists of four transmembrane domains and two connecting extracellular loops (Kalay et al. 2006). The LHFPL5 protein is mainly expressed in the stereocilia of the inner and outer hair cells of the inner ear (Longo-Guess et al. 2005). The LHFPL5 protein serves as an integral component of the mechanotransduction machinery of the cochlea, particularly the stereocilia, where it interacts with the cochlear protein protocadherein-15, which is responsible for applying force to the mechanotransduction channel (Beurg et al. 2015).

Mutational studies involving the 'hurry-scurry' (hscy) mouse model showed that pathogenic sequence variants in the LHFPL5 gene cause severe degeneration of the organ of Corti, thereby resulting in the absence of response to auditory stimuli, as well as circling behavior, constant head shaking from side to side, and the inability to swim (Longo-Guess et al. 2005). A similar phenotype was observed in Drosophila animal models with pathogenic sequence variants in the TMHS gene (Cosetti et al. 2008). To date, less than 10 pathogenic LHFPL5 variants have been reported. These variants are a mix of in-frame (missense) and chain termination (frameshift, splicing) variants (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test has been reported to range from 0.5% to 1.5%. In Japan, 0.5% (1/216) of Japanese deafness patients harbored causative sequence variants in the LHFPL5 gene (Miyagawa et al. 2013). In Algeria, 1.5% (1/65) of families affected by autosomal recessive nonsyndromic hearing impairment and tested negative for pathogenic sequence variants in the GJB2 gene were determined to have disease-causing LHFPL5 variants (Ammar-Khodja et al. 2015).

Testing Strategy

This test provides full coverage of all coding exons of the LHFPL5 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 LHFPL5 test candidates are individuals who present with prelingual, bilateral, severe to profound, stable, autosomal recessive nonsyndromic hearing loss but without vestibular abnormalities. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LHFPL5.

Gene

Official Gene Symbol OMIM ID
LHFPL5 609427
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Recessive 67 AR 610265

Citations

  • Ammar-Khodja F. et al. 2015. Molecular Genetics & Genomic Medicine. 3: 189-96. PubMed ID: 26029705
  • Beurg M. et al. 2015. Proceedings of the National Academy of Sciences of the United States of America. 112: 1589-94. PubMed ID: 25550511
  • Cosetti M. et al. 2008. The Annals of Otology, Rhinology, and Laryngology. 117: 827-33. PubMed ID: 19102128
  • Human Gene Mutation Database (Bio-base).
  • Kalay E. et al. 2006. Human Mutation. 27: 633-9. PubMed ID: 16752389
  • Longo-Guess C.M. et al. 2005. Proceedings of the National Academy of Sciences of the United States of America. 102: 7894-9. PubMed ID: 15905332
  • Miyagawa M. et al. 2013. PLoS One. 8: e71381. PubMed ID: 23967202
  • Shabbir M.I. et al. 2006. Journal of Medical Genetics. 43: 634-40. PubMed ID: 16459341

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

loading Loading... ×

ORDER OPTIONS

An error has occurred while calculating the price. Please try again or contact us for assistance.

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.
Total Price: loading
Patient Prompt Pay Price: loading
A patient prompt pay discount is available if payment is made by the patient and received prior to the time of reporting.
Show Patient Prompt Pay Price
×
Copy Text to Clipboard
×