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Weaver Syndrome via the EZH2 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
8085 EZH2 81236 81236,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8085EZH281236 81236(x1), 81479(x1) $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. 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 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

  • Hannah Cox, PhD

Clinical Features and Genetics

Clinical Features

Weaver syndrome (OMIM 277590) is an overgrowth disorder characterized by tall stature, advanced bone age, macrocephaly, dysmorphic facies, and variable learning disability (Weaver et al. J Pediat 84(4):547-552, 1974; Gibson et al. Am J Hum Genet 90(1):110-118, 2012). Facial features include hypertelorism, large bifrontal diameter, flat occiput, large ears, long philtrum, and retrognathia. Overgrowth is of prenatal onset. Other findings reported include prominent digit pads, thin deep-set nails, umbilical hernia, and scoliosis. Sotos syndrome (OMIM 117550) is an overgrowth disorder with many overlapping features with Weaver syndrome (Opitz et al. Am J Med Genet 79(4):294-304, 1998). A clinical finding that distinguishes Weaver syndrome from Sotos syndrome is retrognathia with a prominent chin crease (Gibson et al., 2012). Conversely, congenital heart disease, renal anomalies, and seizures are more common in Sotos syndrome (Tatton-Brown and Rahman. Am J Med Genet C Semin Med Genet 163(2):86-91, 2013). Although somatic mutations of the EZH2 gene are documented in lymphoid and myeloid malignancies (Ernst et al. Nat Genet 42(8):722-726, 2010; Chase et al. Clin Cancer Res 17(9):2613-2618, 2011, Morin et al. Nat Genet 42(2):181-185, 2010; Nikoloski et al. Nat Genet 42(8):665-667, 2010), cases of Weaver syndrome with constitutional EZH2 mutations and cancer appear to be rare (Tatton-Brown et al. Oncotarget 2(12):1127-1133, 2011).

Genetics

Weaver syndrome due to EZH2 mutations is an autosomal dominant disorder. The majority of pathogenic EZH2 variants are amino acid substitutions and, unlike the NSD1 gene and Sotos syndrome, few truncating mutations have been reported (Tatton-Brown et al., 2011). Mutations are de novo in nearly all cases (Gibson et al., 2012 and Tatton-Brown et al., 2011).

EZH2 (OMIM 601573) encodes a histone methyltransferase and, like NSD1, is a SET domain protein that regulates transcription.

Clinical Sensitivity - Sequencing with CNV PGxome

Analytical sensitivity should be high because all reported EZH2 mutations are expected to be detectable with bi-directional DNA sequencing. Clinical sensitivity is difficult to predict due to the overlapping features with Sotos syndrome. However, with careful phenotypic ascertainment, sensitivity may be high (Tatton-Brown et al. Oncotarget 2(12):1127-1133. 2011).

Thus far, no gross deletions or duplications have been reported in EZH2 (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the EZH2 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

Patients with prenatal onset overgrowth and other clinical features of Weaver syndrome.

Gene

Official Gene Symbol OMIM ID
EZH2 601573
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Weaver Syndrome AD 277590

Citations

  • Chase, A. and Cross, N.C. (2011). "Aberrations of EZH2 in cancer." Clin Cancer Res 17(9):2613-2618. PubMed ID: 21367748
  • Ernst ,T. et al. (2010). "Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders." Nat Genet 42(8):722-726. PubMed ID: 20601953
  • Gibson, W.T. et al. (2011). "Mutations in EZH2 cause Weaver syndrome." Am J Hum Genet 90(1):110-118. PubMed ID: 22177091
  • Human Gene Mutation Database (Bio-base).
  • Morin, R.D. et al. (2010). "Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin." Nat Genet. 42(2):181-185. PubMed ID: 20081860
  • Nikoloski, G. et al. (2010). "Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes." Nat Genet 42(8):665-667. PubMed ID: 20601954
  • Opitz, J. M. et.al. (1998). "The syndromes of Sotos and Weaver: reports and review." Am J Med Genet 79(4): 294-304. PubMed ID: 9781911
  • Tatton-Brown, K. and Rahman, N. (2013). "The NSD1 and EZH2 overgrowth genes, similarities and differences."  Am J Med Genet C Semin Med Genet 163(2):86-91. PubMed ID: 23592277
  • Tatton-Brown, K. et al. (2011). "Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height." Oncotarget 2(12):1127-1133. PubMed ID: 22190405
  • Weaver, D. D. (1974). "A new overgrowth syndrome with accelerated skeletal maturation, unusual facies, and camptodactyly." J Pediat 84(4):547-552. PubMed ID: 4366187

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.
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