Idiopathic Hypogonadotropic Hypogonadism (IHH) via the GNRHR 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 | |
---|---|---|---|---|---|
9113 | GNRHR | 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
Idiopathic hypogonadotropic hypogonadism (IHH) is a group of reproductive disorders due to gonadotropin-releasing hormone (GnRH) deficiency (Layman 2013). IHH is characterized by absent or incomplete pubertal development, low levels of circulating gonadotropins and testosterone, and no other abnormalities of the hypothalamic-pituitary axis. IHH can be divided into two major phenotypes: normosmic hypogonadotropic hypogonadism (nHH), in which hypothalamic GnRH gene regulation or GnRH synthesis, secretion, or signaling is impaired; and Kallmann syndrome (KS), in which this migratory pathway of GnRH and olfactory neurons from the nasal region into the hypothalamus is disrupted. Defects in the GnRH receptor encoded by the GNRHR gene cause nHH.
Genetics
GNRHR-associated nHH is an autosomal recessive disorder (Layman 2013; Layman et al. 1998; de Roux N et al. 1997). The GNRHR gene has 3 coding exons that encode the GnRH receptor. Genetic defects in GNRHR include missense (vast majority), nonsense, splicing site mutations, small indels and exon-level large deletion/duplications (Human Gene Mutation Database).
Clinical Sensitivity - Sequencing with CNV PGxome
The prevalence of GNRHR mutations has been estimated to be approximately 5% in normosmic hypogonadotropic hypogonadism (nHH) patients (Layman 2013).
The rate of deletion/duplication pathogenic variants in the GNRHR gene in a large cohort of patients with idiopathic hypogonadotropic hypogonadism is currently unknown.
Testing Strategy
This test provides full coverage of all coding exons of the GNRHR 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
Candidates for this test are patients with autosomal recessive normosmic hypogonadotropic hypogonadism (nHH). Testing is also indicated for family members of patients who have known GNRHR mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GNRHR.
Candidates for this test are patients with autosomal recessive normosmic hypogonadotropic hypogonadism (nHH). Testing is also indicated for family members of patients who have known GNRHR mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GNRHR.
Gene
Official Gene Symbol | OMIM ID |
---|---|
GNRHR | 138850 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Disease
Name | Inheritance | OMIM ID |
---|---|---|
Hypogonadotropic Hypogonadism 7 with or without Anosmia | AR | 146110 |
Citations
- de Roux N, Young J, Misrahi M, Genet R, Chanson P, Schaison G, Milgrom E. 1997. A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor. New England Journal of Medicine 337: 1597-1603. PubMed ID: 9371856
- Human Gene Mutation Database (Bio-base).
- Layman LC, Cohen DP, Jin M, Xie J, Li Z, Reindollar RH, Bolbolan S, Bick DP, Sherins RR, Duck LW, Musgrove LC, Sellers JC, Neill JD. 1998. Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism. Nat. Genet. 18: 14-15. PubMed ID: 9425890
- Layman LC. 2013. The genetic basis of female reproductive disorders: etiology and clinical testing. Mol. Cell. Endocrinol. 370: 138–148. PubMed ID: 23499866
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.