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Hirschsprung Disease (HSCR) via the RET 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
11619 RET 81406 81406,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11619RET81406 81406(x1), 81479(x1) $890 Order Options and Pricing

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).

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

  • Greg Fischer, PhD

Clinical Features and Genetics

Clinical Features

Hirschsprung disease (HSCR) (OMIM# 142623), aka congenital intestinal aganglionosis, is a birth defect characterized by complete absence of neuronal ganglion cells from a portion of the intestinal tract (Eng & Mulligan. Hum Mutat 9:97-109, 1997). In 80% of individuals, aganglionosis is restricted to the rectosigmoid colon (S-HSCR); in 15%-20%, aganglionosis extends beyond the sigmoid colon (L-HSCR); in about 5%, aganglionosis affects the entire large intestine (total colonic aganglionosis). HSCR is the main genetic cause of functional intestinal obstruction in infants and children. Affected infants frequently present in the first two months of life with symptoms of impaired intestinal motility, such as failure to pass meconium within the first 48 hours of life, constipation, emesis, abdominal pain or distention, and occasionally diarrhea. However, because the initial diagnosis of HSCR may be delayed, HSCR should be considered in anyone with lifelong severe constipation.

Genetics

Hirschsprung disease (HSCR) has an estimated incidence of 1 in 5,000 births, varying among different ethnic groups. About 70% of affected individuals have the nonsyndromic form (isolated HSCR), and the remaining 30% have the syndromic form with multiple congenital abnormalities. At least six different genes are associated with isolated HSCR, with different inheritance patterns (Parisi GeneReview 2006). RET is the primary gene underlying HSCR, and RET-related HSCR is inherited in an autosomal dominant manner with reduced and sex-dependent penetrance (Passarge Nat Genet 31:11-12, 2002). Loss-of-function variants in RET have been identified in 50% familial and 10-35% of sporadic HSCR cases. The RET proto-oncogene is one of the receptor tyrosine kinases, cell-surface molecules that transduce signals for cell growth and differentiation. This gene plays a crucial role in neural crest development. RET interacts with the glial-derived neurotropic factor (GDNF) family of ligands: GDNF, neurturin, persephin, and artemin. Formation of a complex containing two RET protein molecules leads to RET autophosphorylation and intracellular signaling (Santoro et al. Endocrinology 145:5448-5451, 2004).

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect disease variants in 50% of familial HSCR cases and up to 35% of sporadic HSCR cases (Attie et al. Hum Mol Genet 4:1381-1386, 1995; Eng & Mulligan. Hum Mutat 9:97-109, 1997, Hofstra et al. Hum Mutat 15:418-429, 2000; Bolk Gabriel et al. Nature Genet 31:89-93, 2002). Among individuals with L-HSCR, a RET variant can be detected in as high as 80% of cases (Angrist et al. Hum Mol Genet 4:821-830, 1995, Seri et al. Hum Mutat 9:243-249, 1997).

Testing Strategy

This test provides full coverage of all coding exons of the RET 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 clinical features consistent with nonsyndromic HSCR and family members of patients who have known RET variants.

Gene

Official Gene Symbol OMIM ID
RET 164761
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Hirschsprung Disease 1 AD 142623

Citations

  • Angrist, M., et.al. (1995). "Mutation analysis of the RET receptor tyrosine kinase in Hirschsprung disease." Hum Mol Genet 4(5): 821-30. PubMed ID: 7633441
  • Attie, T., et.al. (1995). "Diversity of RET proto-oncogene mutations in familial and sporadic Hirschsprung disease." Hum Mol Genet 4(8): 1381-6. PubMed ID: 7581377
  • Eng C, Mulligan LM. 1997. Mutations of the RET proto-oncogene in the multiple endocrine neoplasia type 2 syndromes, related sporadic tumours, and hirschsprung disease. Hum. Mutat. 9: 97–109. PubMed ID: 9067749
  • Gabriel, S. B., et.al. (2002). "Segregation at three loci explains familial and population risk in Hirschsprung disease." Nat Genet 31(1): 89-93. PubMed ID: 11953745
  • Hofstra, R. M., et.al. (2000). "RET and GDNF gene scanning in Hirschsprung patients using two dual denaturing gel systems." Hum Mutat 15(5): 418-29. PubMed ID: 10790203
  • Parisi MA. 2011. Hirschsprung Disease Overview. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301612
  • Passarge, E. (2002). "Dissecting Hirschsprung disease." Nat Genet 31(1): 11-2. PubMed ID: 11953748
  • Santoro M. 2004. Minireview: RET: Normal and Abnormal Functions. Endocrinology 145: 5448–5451. PubMed ID: 15331579
  • Seri, M., et.al. (1997). "Frequency of RET mutations in long- and short-segment Hirschsprung disease." Hum Mutat 9(3): 243-9. PubMed ID: 9090527

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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