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Male Infertility with Large-Headed Spermatozoa via the AURKC 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
8669 AURKC 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8669AURKC81479 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Fang Xu, PhD, FACMG

Clinical Features and Genetics

Clinical Features

More than one million couples worldwide seek reproductive assistance each year (Chandra et al. 2005; Nyboe Andersen et al. 2009). In half the cases, male infertility is a major contributing factor. Common causes of male infertility include little or no sperm in the semen (i.e. azoospermia and oligozoospermia), low sperm motility (i.e. asthenozoospermia), and abnormal sperm morphology (i.e. teratozoospermia) (Cooke and Saunders 2002). Male infertility associated with large-headed, multiflagellar, polyploid spermatozoa is a classic teratozoospermia condition, characterized by a high percentage (30-100%) of bulky, irregular-shaped spermatozoa in the patient’s semen (German et al. 1981). In these patients, most spermatozoon heads have 2-4 times the normal DNA content and up to 6 distinct tails (Devillard et al. 2002). While intracytoplasmic sperm injection (ICSI) has been used to effectively treat patients exhibiting >30% large-headed spermatozoa, the pregnancy rate per transfer is low (~15%) and the risk of chromosomal abnormalities and perinatal death is higher than normal (Achard et al. 2007). As a result, the financial burdens and emotional stress of reproductive assistance is even greater for these patients.

Genetics

In a cohort of 14 unrelated infertile men of African descent with a large-headed sperm phenotype, Dieterich and colleagues identified a homozygous cytosine (C) deletion in exon 3 (c.144delC) of the Aurora-C kinase (AURKC) gene, which encodes a conserved protein kinase responsible for chromosomal segregation during mitosis (Dieterich et al. 2007). In a subsequent study (Dieterich et al. 2009), the same group reported that of 32 patients with infertility and large-headed sperm, 31 were homozygous for the AURKC c.144delC variant while one patient was heterozygous for c.144delC and heterozygous for a novel AURKC missense variant p.Cys229Tyr. Women homozygous for c.144delC were healthy and had no problem conceiving naturally. Men heterozygous for a single AURKC variant were also unaffected. From these studies, it was estimated that, in North African populations, the allele frequency of c.144delC is ~2%, and the prevalence of AURKC-associated infertility is 1/10,000 men. Currently, the prevalence of AURKC-associated infertility in other ethnic groups is not known.

Clinical Sensitivity - Sequencing with CNV PGxome

The sensitivity of this test is predicted to be nearly 100% for infertile men with a “typical” large-headed sperm phenotype (see Dieterich et al. Hum Mol Genet 18:1301-1309, 2009).

Testing Strategy

This test provides full coverage of all coding exons of the AURKC 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 men with infertility and a high percentage (30-100%) of large headed sperm as well as relatives of patients with a known AURKC variant. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in AURKC.

Gene

Official Gene Symbol OMIM ID
AURKC 603495
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Achard, V., et.al. (2007). "Reproductive failure in patients with various percentages of macronuclear spermatozoa: high level of aneuploid and polyploid spermatozoa." J Androl 28(4): 600-6. PubMed ID: 17412686
  • Chandra, A., et.al. (2005). "Fertility, family planning, and reproductive health of U.S. women: data from the 2002 National Survey of Family Growth." Vital Health Stat 23 (25): 1-160. PubMed ID: 16532609
  • Cooke, H. J., Saunders, P. T. (2002). "Mouse models of male infertility." Nat Rev Genet 3(10): 790-801. PubMed ID: 12360237
  • Devillard, F., et.al. (2002). "Polyploidy in large-headed sperm: FISH study of three cases." Hum Reprod 17(5): 1292-8. PubMed ID: 11980754
  • Dieterich, K., et.al. (2007). "Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility." Nat Genet 39(5): 661-5. PubMed ID: 17435757
  • Dieterich, K., et.al. (2009). "The Aurora Kinase C c.144delC mutation causes meiosis I arrest in men and is frequent in the North African population." Hum Mol Genet 18(7): 1301-9. PubMed ID: 19147683
  • German, J (1981). "Thirty-second annual meeting, American Society of Human Genetics. October 28-31, 1981, Dallas. Abstracts." Am J Hum Genet 33(6): 64A. PubMed ID: 6119901
  • Nyboe Andersen, A., et.al. (2009). "Assisted reproductive technology and intrauterine inseminations in Europe, 2005: results generated from European registers by ESHRE: ESHRE. The European IVF Monitoring Programme (EIM), for the European Society of Human Reproduction and Embryology (ESHRE)." Hum Reprod 24(6): 1267-87. PubMed ID: 19225009

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

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ORDER OPTIONS

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View Ordering Instructions

1) Select Test Method (Platform)


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.
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