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Hypogonadotropic Hypogonadism/Kallmann Syndrome via the FEZF1 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
7959 FEZF1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7959FEZF181479 81479,81479 $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.

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

  • Fang Xu, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Kallmann syndrome (KS) is a genetic disorder characterized by delayed or absent puberty along with an impaired or absent sense of smell (hyposmia or anosmia). This disorder is a form of idiopathic hypogonadotropic hypogonadism (IHH), which is a group of reproductive conditions due to gonadotropin-releasing hormone (GnRH) deficiency (Dodé and Hardelin. 2009. PubMed ID: 18985070; Layman. 2013. PubMed ID: 23650337). Patients with IHH usually present with absent or incomplete pubertal development, low levels of circulating gonadotropins LH (luteinizing hormone) and FSH (follicle-stimulating hormone), but 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 the migratory pathway of GnRH and olfactory neurons from the nasal region into the hypothalamus is disrupted.

Due to hypothalamic GnRH deficiency, infant boys with KS often demonstrate micropenis and cryptorchidism. Adult males with KS present failure to undergo normal puberty and absence of secondary sexual characteristics. Females with KS usually present with primary amenorrhea or infertility. The lack of the sense of smell is the key feature that distinguishes Kallmann syndrome from other forms of hypogonadotropic hypogonadism. The degree of both the hypogonadism and the smell deficiency vary significantly even within affected family members. In addition to reproductive symptoms, many KS patients exhibit a wide variety of additional signs and symptoms. Commonly recognized non-reproductive features that may be present in KS patients include: digital synkinesia, unilateral renal agenesis, cleft lip and/or palate, dental agenesis, hearing loss, and abnormal eye movements (Kaplan et al. 2010. PubMed ID: 20949504; Layman. 2013. PubMed ID: 23650337; Balasubramanian et al. 2017. PubMed ID: 20301509).

Genetics

To date, more than ten different genes have been identified to cause KS and nHH (Layman. 2013. PubMed ID: 23650337). FEZF1-related KS is inherited in an autosomal recessive manner. FEZF1, which encode a transcriptional repressor, is one of the genes. FEZF1 is a zinc-finger gene encoding a transcriptional factor. It is highly and selectively present during embryogenesis in the olfactory epithelium, amygdala, and hypothalamus. Fezf1-deficient mice have shown impaired axonal projection of pioneer olfactory receptor neurons (ORNs) (Hirata et al. 2006. PubMed ID: 16971467). Homozygous missense variants and a small deletion in FEZF1 have been found in patients with KS (Kotan et al. 2014. PubMed ID: 25192046).

Clinical Sensitivity - Sequencing with CNV PGxome

To date, only two pathogenic variants have been reported in FEZF1 (Kotan et al. 2014. PubMed ID: 25192046). Abnormalities in FEZF1 therefore appear to be a relatively rare cause of disease.

Testing Strategy

This test provides full coverage of all coding exons of the FEZF1 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 symptoms consistent with hypogonadotropic hypogonadism/Kallmann syndrome. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in FEZF1.

Gene

Official Gene Symbol OMIM ID
FEZF1 613301
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Hypogonadotropic Hypogonadism/Kallmann Syndrome Panel

Citations

  • Balasubramanian et al. 2017. PubMed ID: 20301509
  • Dodé and Hardelin. 2009. PubMed ID: 18985070
  • Hirata et al. 2006. PubMed ID: 16971467
  • Kaplan et al. 2010. PubMed ID: 20949504
  • Kotan et al. 2014. PubMed ID: 25192046
  • Layman. 2013. PubMed ID: 23650337

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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