Deafness, Autosomal Recessive 39 (DFNB39) via the HGF 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
11373 HGF 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11373HGF81479 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 39 (DFNB39) is characterized by prelingual, bilateral, severe to profound, nonprogressive, sensorineural nonsyndromic hearing loss (Wajid et al. 2003). 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 audiometery of DFNB39 individuals usually show a downward-sloping audiogram, indicating hearing loss affecting all frequencies, with more severe impairment for high frequencies (Schultz et al. 2009).

Genetics

DFNB39 is an autosomal recessive hearing disorder that is caused by pathogenic sequence variants in the hepatocyte growth factor (HGF) gene. The HGF gene is located in chromosomal region 7q21.11 and consists of 18 coding exons (Weidner et al. 1991; Wajid et al. 2003). The HGF protein is ubiquitously expressed and is involved in various signalling pathways, mainly acting as a mitogen that stimulates the growth of various cells such as hepatocytes and lung fibroblasts, as well as placental and cochlear cells (Gohda et al. 1988). The HGF protein has several isoforms. HGF isoform-1 encodes a preprotein that is cleaved into two chains: the alpha chain consists of a hairpin loop and four N-terminal kringle domains; the beta chain is homologous to trypsin-like proteases although it has no catalytic function (Schultz et al. 2009). HGF isoform-2 encodes two kringle domains, and HGF isoform-3 and isoform-4 are similar to 1 and 2, except for the existence of an alternate exon 5b splice acceptor site. Previous studies using mouse models have shown that disease-causing variants in the HGF gene result in the overexpression of the HGF protein, which has been associated with progressive degeneration of the outer hair cells of the cochlea (Schultz et al. 2009). On the other hand, deletion of the HGF gene in these mouse models results in general dysplasia. To date, fewer than 10 pathogenic HGF sequence variants have been reported, which include 1 splicing and 2 regulatory sequence variants that cause nonsyndromic hearing loss, and 2 truncating and 2 missense variants that cause lymphoedema (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

In a comprehensive study on autosomal recessive nonsyndromic hearing loss cases in Iran, 0.7% (1/144) of families harbored pathogenic sequence variants in the HGF gene (Babanejad et al. 2012).

No large-scale studies have been conducted on copy number changes involving the HGF gene. No large deletions or duplications of HGF have been documented as pathogenic for hearing loss.

Testing Strategy

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

Gene

Official Gene Symbol OMIM ID
HGF 142409
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Recessive 39 AR 608265

Citations

  • Babanejad M. et al. 2012. American Journal of Medical Genetics. Part A. 158A: 2485-92. PubMed ID: 22903915
  • Gohda E. et al. 1988. The Journal of Clinical Investigation. 81: 414-9. PubMed ID: 3276728
  • Hildebrand M.S. et al. 2008. Genetics in Medicine. 10: 797-804. PubMed ID: 18941426
  • Human Gene Mutation Database (Bio-base).
  • Schultz J.M. et al. 2009. American Journal of Human Genetics. 85: 25-39. PubMed ID: 19576567
  • Wajid M. et al. 2003. European Journal of Human Genetics : Ejhg. 11: 812-5. PubMed ID: 14512973
  • Weidner K.M. et al. 1991. Proceedings of the National Academy of Sciences of the United States of America. 88: 7001-5. PubMed ID: 1831266

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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