Deafness, Autosomal Recessive 39 (DFNB39) via the HGF Gene
Summary and Pricing
Test Method
Exome Sequencing with CNV DetectionTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
11373 | HGF | 81479 | 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.
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.
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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
PGxome (Exome) Sequencing Panel
PGnome (Genome) Sequencing Panel
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.