Horizon Clinician Information | Natera

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Horizon carrier screening experience across 380,000+ patients


The Horizon difference


Clinical features

  • Horizon screens for 274 conditions. The five-panel and à la carte ordering options enable you to screen for just what the guidelines recommend or for a broad number of conditions.
  • Horizon is one of the first tests to screen for Duchenne muscular dystrophy (DMD). DMD is more common than SMA and fragile X and has an incidence similar to cystic fibrosis.
  • Horizon refines your patients’ risks. Fragile X automatic AGG interruption testing, enhanced spinal muscular atrophy (SMA) screening, and Tay-Sachs enzyme testing provide you with more information than standard screening.

Learn more: Download SMA White Paper

Learn more: Download DMD White Paper

 


Why offer screening for inherited conditions?

When two people are carriers for the same autosomal-recessive condition, they have a 25% chance of having an affected child during each pregnancy. For X-linked conditions, only the mother needs to be a carrier for there to be a risk of passing on the condition to the child. Knowing their carrier status allows couples to consider pre-pregnancy reproductive options such as preimplantation genetic diagnosis (PGD) or plan for the birth of a child with a genetic condition.


 

Following best practices

Horizon was developed to allow healthcare providers to offer carrier screening for conditions that are currently recommended by the following professional medical societies:

  • The American College of Medical Genetics and Genomics (ACMG)
  • The American Congress of Obstetricians and Gynecologists (ACOG)
  • The Victor Center for the Prevention of Jewish Genetic Diseases

Each organization recommends screening the general population or specific ethnic groups for certain conditions, based on carrier frequencies, incidence rates, and other criteria. Learn more about screening recommendations.


Product support

  • Horizon can be used with both saliva and blood samples. Kits can be stored in your office at room temperature. We provide complimentary, on-demand shipping to and from your clinic.
  • Genetic counselors are here to support your practice. At no additional cost, board-certified genetic counselors are available to answer any questions about Horizon that you or your patients may have.
  • Tools and resources are available throughout the process, including mobile phlebotomy services, patient and physician portals, and EMR integration.

 

 


Panel options for every patient

Panels / Number of conditions Suitable for
Horizon 4 Patients of any ethnic background
Horizon 14 Patients of any ethnic background
Horizon 27 Patients of any ethnic background
Horizon 106 Patients of Ashkenazi or Sephardic Jewish descent
Horizon 274 Patients of any ethnic background OR Jewish patients who prefer more coverage than Horizon 106
A la Carte: Cystic Fibrosis, Spinal Muscular Atrophy, and/or Tay-Sachs Enzyme Patients of any ethnic background

 

View Conditions by Panel


Combined methodologies, improved sensitivity

Horizon uses various methodologies to identify carriers of different types of genetic variants. These methods are often used in combination to increase test sensitivity. Horizon employs the following methods:


Combined Methodologies

Copy number analysis

Variations in the number of copies of certain genes or regions of genes can have clinical implications. Several methods may be used to detect variations in copy number, including multiplex ligation-dependent probe amplification and fluorescent quantitative polymerase chain reaction (PCR). These methodologies can be used to identify deletions and duplications or to quantify the amount of DNA present in a region of interest.

Next-generation sequencing

The sequenced DNA is compared to a reference genome to identify any variation. The significance of any variants is determined based upon a combination of several sources of information, including current knowledge of the variants themselves and predicted effects of the variation upon gene function. In accordance with ACMG guidelines, only variants determined to be pathogenic or likely pathogenic are reported. Variants determined to be benign or of uncertain clinical significance are not reported.

Polymerase chain reaction

Polymerase chain reaction (PCR) is a process by which a small region of DNA is cloned and amplified for the purpose of sequencing. By amplifying a specific region of DNA, multiple copies of the area of interest are available for DNA analysis. A type of PCR, in conjunction with capillary electrophoresis, is performed for detection of carriers of fragile X syndrome.

Genotyping

Genotyping may be performed for genes and regions of DNA that are not amenable to next-generation sequencing. It may also be used for purposes of quality control.

Sanger sequencing

Sanger sequencing is used as appropriate to confirm the presence of genetic variants identified using other methods. This method allows for an in-depth look at specific regions of DNA.

More information

Contact us for descriptions of the methods used for specific conditions. Carrier rates, detection rates, and residual risk rates are available.

Contact Us


What if My Patient is a Carrier

Non-pregnant Carriers: Recessive Conditions

If your patient is a carrier for a specific autosomal recessive condition it is recommended that the partner be screened for the same condition. If the partner is a carrier for the same condition, referral for formal genetic counseling should be considered. Couples at risk to have a baby with an autosomal recessive disease can consider several reproductive options including:

  • natural pregnancy, with or without prenatal diagnosis
  • preimplantation genetic diagnosis (PGD) with in vitro fertilization (IVF) to test and then transfer embryos that are free of the condition
  • the use of a sperm or egg donor
  • adoption

Non-pregnant Carriers: X-Linked Conditions

Partner screening is not often recommended as a next step for carriers for of X-linked conditions because only the mother needs to be a carrier for the condition to be passed to the child. You may wish to discuss available reproductive options with your patient, including preimplantation genetic diagnosis (PGD) with in vitro fertilization (IVF), adoption, using an egg donor, or prenatal diagnosis.

Pregnant Carriers: Recessive Conditions

If your patient is a carrier for a specific autosomal recessive condition it is recommended that the partner be screened for the same condition. If the partner is a carrier for the same condition, referral for formal genetic counseling should be considered. Couples at risk to have a baby with an autosomal recessive disease can consider invasive prenatal diagnosis using chorionic villus sampling or amniocentesis. Alternatively, the couple may choose to delay testing until after delivery.

Pregnant Carriers: X-Linked Conditions

If your patient is pregnant and found to be a carrier for an X-linked recessive condition, referral for genetic counseling should be suggested. Fetal gender can be confirmed using Panorama, a simple blood test from the mother. Alternatively, some couples will choose to have a diagnostic test such as chorionic villus sampling or amniocentesis. Diagnostic testing can also be performed after the baby is delivered.


The Horizon Process

Physician orders Horizon

Blood or saliva sample collected

Sample shipped to Natera and analyzed

Results sent to physician in about 2 weeks


References

  1. Punnoose, AR, Golub, RM MD. Muscular Dystrophy. JAMA. 2011 ;306(22):2526.
  2. Edwards, Janice G. MS; Feldman, Gerald MD, PhD; Goldberg, James MD; Gregg, Anthony R. MD; Norton, Mary E. MD; Rose, Nancy C. MD; Schneider, Adele MD; Stoll, Katie MS; Wapner, Ronald MD; Watson, Michael S. MD Expanded Carrier Screening in Reproductive Medicine-Points to Consider: A Joint Statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine Obstetrics & Gynecology: March 2015 - Volume 125 - Issue 3 - p 653-662
  3. Committee Opinion No. 469: Carrier Screening for Fragile X Syndrome. Obstetrics & Gynecology. 2010;116(4): 1008-1010.
  4. National Newborn Screening and Genetics Resource Center. National Newborn Screening Report 10-Year Incidence Report 1991-2000. San Antonio, TX: National Newborn Screening and Genetics Resource Center, 2003.
  5. Cyrulnik SE, Fee RJ, Batchelder A, Kiefel J, Goldstein E, Hinton VJ. Cognitive and adaptive deficits in young children with Duchenne muscular dystrophy (DMD). J Int Neuropsychol Soc. 2008 Sep;14(5):853-61.
  6. Yiu EM1, Kornberg AJ. Duchenne muscular dystrophy .J Paediatr Child Health. 2015 Mar 9.
  7. American Academy of Pediatrics Clinical Report: Cardiovascular Health Supervision for Individuals Affected by Duchenne or Becker Muscular Dystrophy. Pediatrics 2005 Dec; 116 (6).
  8. Yazaki M, Yoshida K, Nakamura A et al. Clinical Characteristics of Aged Becker Muscular Dystrophy Patients with Onset after 30 Years. Eur Neurol. 1999;42(3):145-149.
  9. Bushby KM. The limb-girdle muscular dystrophies-multiple genes, multiple mechanisms. Hum Mol Genet. 1999;8:1875-82.
  10. Dent KM, Dunn DM, von Niederhausern AC, Aoyagi AT, Kerr L, Bromberg MB, Hart KJ, Tuohy T, White S, den Dunnen JT, Weiss RB, Flanigan KM. Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort. Am J Med Genet A. 2005;134:295-8.
  11. Grimm T, Kress W, Meng G, MOiier CR. Risk assessment and genetic counseling in families with Duchenne muscular dystrophy. Acta Myol. 2012 Dec;31 (3):179-8.
  12. Flanigan KM, Dunn DM, von Niederhausern A, Soltanzadeh P, Gappmaier E, Howard MT, Sampson JB, Mendell JR, Wall C, King WM, Pestronk A, Florence JM, Connolly AM, Mathews KD, Stephan CM, Laubenthal KS, Wong BL, Morehart PJ, Meyer A, Finkel RS, Bonnemann CG, Hinton VJ, De Vivo DC, Nereo NE, Goldstein E, Stern Y. Selective deficits in verbal working memory associated with a known genetic etiology: the neuropsychological profile of duchenne muscular dystrophy. J Int Neuropsychol Soc. 2001; 7: 45-54.
  13. Ciafaloni E1, Fox DJ, Pandya S, Westfield GP, Puzhankara S, Romitti PA, Mathews KD, Miller TM, Matthews DJ, Miller LA, Cunniff C, Druschel CM, Moxley RT. Delayed diagnosis in duchenne muscular dystrophy: data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). J Pediatr. 2009 Sep; 155(3):380-5.
  14. Bermúdez-López C1, Garcia-de Teresa B, González-del Angel A, Alcántara-Ortigoza MA. Germinal mosaicism in a sample of families with Duchenne/Becker muscular dystrophy with partial deletions in the DMD gene. Genet Test Mol Biomarkers. 2014 Feb;18(2):93-7. doi: 10.1089/gtmb.2013.0384. Epub 2013 Nov 16.
  15. Schade van Westrum SM1, Hoogerwaard EM, Dekker L, Standaar TS, Bakker E, lppel PF, Oosterwijk JC, Majoor-Krakauer DF, van Essen AJ, Leschot NJ, Wilde AA, de Haan RJ, de Visser M, van der Kooi AJ. Cardiac abnormalities in a follow-up study on carriers of Duchenne and Becker muscular dystrophy. Neurology. 2011 Jul 5;77(1):62-6.
  16. Brioschi S, Gualandi F, Scotton C, Armaroli A, Bovolenta M, Falzarano MS, Sabatelli P, Selvatici R, D'Amico A, Pane M, Ricci G, Siciliano G, Tedeschi S, Pini A, Vercelli L, De Grandis D, Mercuri E, Bertini E, Merlini L, Mongini T, Ferlini A. Genetic characterization in symptomatic female DMD carriers: lack of relationship between X-inactivation, transcriptional DMD allele balancing and phenotype. BMC Med Genet. 2012 Aug 16;13:73.
  17. Mercier S, Toutain A, Toussaint A et al. Genetic and clinical specificity of 26 symptomatic carriers for dystrophinopathies at pediatric age. Eur J Hum Genet. 2013;21 (8):855-863.
  18. Darras BT, Miller DT, Urion DK. Dystrophinopathies. GeneReviews, Updated November 26, 2014.­­­­­