Deafness, Autosomal Recessive 77 (DFNB77) via the LOXHD1 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
4287 LOXHD1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4287LOXHD181479 81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

Clinical Features

Autosomal recessive deafness 77 (DFNB77) is characterized by moderate to profound, progressive, postlingual nonsyndromic hearing loss. 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). Individuals with DFNB77 generally have intact low-frequency hearing and mild to moderate mid-frequency (500-2,000 Hz) and high-frequency (>2,000 Hz) hearing loss (Grillet al. 2009). The onset of disease occurs at 7-8 years of age, progressing to moderate to profound hearing loss during adulthood. Affected individuals have normal vestibular function, thus achieving age-appropriate developmental milestones such as sitting and walking, without issues of tinnitus, balance disorders, or vertigo.

Genetics

DFNB77 is an autosomal recessive hearing disorder that is caused by pathogenic sequence variants in the lipoxygenase homology domain-containing 1 (LOXHD1) gene, which is mainly expressed in the cochlear and vestibular hair cells of the inner ear, particularly along the length of stereocilia (Grillet et al. 2009). The LOXHD1 gene is located in chromosome 18q12-q21 and consists of 40 coding exons that encode a 2,211-amino acid protein (Riazuddin et al. 2012). The LOXHD1 protein consists of 15 polycystin/lipoxygenase/alpha-toxin domains, which are 120-amino acid regions that are postulated to interact with the plasma membrane as well as other proteins, thereby providing mechanosensory roles in the apical surface of hair cells of the inner ear (Muller and Grillet 2010).

To date, a total of less than 10 pathogenic LOXHD1 sequence variants have been reported to cause sensorineural nonsyndromic hearing loss, which include 7 truncating and 1 splicing variants (Human Gene Mutation Database). Individuals with causative sequence variants in the LOXHD1 gene have been associated with poor cochlear implant performance (Eppsteiner et al. 2012). Around 15 pathogenic missense sequence variants in the LOXHD1 gene have also been linked to late-onset Fuchs corneal dystrophy, a disorder that affects the corneal endothelium, often resulting in the need for corneal transplantation (Sundin et al. 2006).

Clinical Sensitivity - Sequencing with CNV PG-Select

The clinical sensitivity of this test has been reported to range up to 8%. For example, two independent investigations conducted in Japan indicated that pathogenic sequence variants in the LOXHD1 gene accounted for 0.3% (3/1,120 and 4/1,314) of nonsyndromic hearing loss cases (Nishio and Usame 2015; Mori et al. 2015). Disease-causing LOXHD1 variants were detected in 1.3% (2/160) of families from Turkey, Iran, Mexico, Ecuador, and Puerto Rico with autosomal recessive nonsyndrome deafness (Bademci et al. 2015). In a study involving Iranian consanguineous families with autosomal recessive nonsydromic hearing loss, 6.7% (2/30) harbored causative LOXHD1 sequence variants (Diaz-Horta et al. 2015). In another research investigation, disease-causing LOXHD1 sequence variants were detected in 8.3% (1/12) of families from Ital and Qatar with hearing impairment (Vozzi et al. 2014).

Testing Strategy

This test provides full coverage of all coding exons of the LOXHD1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

The ideal LOXHD1 test candidates are individuals who present with moderate to profound, progressive, postlingual, mid- to high-frequency autosomal recessive nonsyndromic hearing loss. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LOXHD1.

Gene

Official Gene Symbol OMIM ID
LOXHD1 613072
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Recessive 77 AR 613079

Citations

  • Bademci G. et al. 2015. Genetics in Medicine : Official Journal of the American College of Medical Genetics. 0: N/A. PubMed ID: 26226137
  • Diaz-Horta O. et al. 2012. Plos One. 7: e50628. PubMed ID: 23226338
  • Eppsteiner RW. et al. 2012. Hearing Research. 292: 51-8. PubMed ID: 22975204
  • Grillet N. et al. 2009. American Journal of Human Genetics. 85: 328-37. PubMed ID: 19732867
  • Hildebrand M.S. et al. 2008. Genetics in Medicine. 10:797-804. PubMed ID: 18941426
  • Human Gene Mutation Database (Bio-base).
  • Mori K. et al. 2015. The Annals of Otology, Rhinology, and Laryngology. 124 Suppl 1: 135S-41S. PubMed ID: 25792669
  • Müller U., Grillet N. 2010. Future Neurology. 5: 9-12. PubMed ID: 24436636
  • Nishio S.Y., Usami S. 2015. The Annals of Otology, Rhinology, and Laryngology. 124 Suppl 1: 49S-60S. PubMed ID: 25788563
  • Riazuddin SA. et al. 2012. American Journal of Human Genetics. 90: 533-9. PubMed ID: 22341973
  • Sundin OH. et al. 2006. Investigative Ophthalmology & Visual Science. 47: 3919-26. PubMed ID: 16936105
  • Vozzi D. et al. 2014. Gene. 542: 209-16. PubMed ID: 24657061

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.

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

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ORDER OPTIONS

View Ordering Instructions

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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.

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