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Perlman Syndrome via the DIS3L2 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
DIS3L2 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9851DIS3L281479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

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.


Genetic Counselors


  • Eric Bend, PhD

Clinical Features and Genetics

Clinical Features

Perlman Syndrome is a congenital overgrowth disorder that is characterized by macrosomia, visceromegaly, macrocephaly, polyhydramnios, dysmorphic facial features, pancreatic hyperplasia, neurodevelopmental delay, and nephroblastomatosis with an increased risk for Wilms tumor at an early age (Alessandri et al. 2008; Astuti et al. 2012). Dysmorphic facial features include depressed nasal bridge, prominent everted upper lip, low set ears, deep set eyes and a prominent forehead (Morris et al. 2013). It can be suspected prenatally by evidence of cystic hygroma, nuchal luceny, macrosomia, enlarged kidneys, renal anomalies (hamartoma and Wilms tumor), and visceromegaly. It is a rare disorder with an incidence of 1 in 1,000,000 (http://www.orpha.net/). The prognosis of Perlman syndrome is poor with a high mortality rate, often due to renal failure, hypoxemia, pulmonary hypoplasia and hypoglycemia (Morris et al. 2013). Differential diagnosis includes other overgrowth disorders, such as Beckwith-Wiedemann, Simpson-Golabi-Behmel, Sotos and Weaver syndromes.


Perlman syndrome is inherited in an autosomal recessive manner, and is caused by pathogenic variants in the DIS3L2 gene. This gene encodes an exonuclease and is thought to have a role in cellular RNA metabolism (Lubas et al. 2013). Pathogenic variants are found in the RNA-binding (RNB) domain, which may lead to disrupted exonuclease activity (Astuti et al. 2012; Morris et al. 2013). DIS3L2 inactivation by pathogenic variants is also associated with mitotic abnormalities, and interestingly knockdown of this gene enhances cellular growth (Astuti et al. 2012). Reported pathogenic variants include missense, splicing and gross deletions (Astuti et al. 2012; Higashimoto et al. 2013).

Clinical Sensitivity - Sequencing with CNV PG-Select

Although the clinical sensitivity is not known, it should be high since the DIS3L2 gene is the only gene that is known to be associated with Perlman Syndrome. Gross heterozygous deletions may not be detected via sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the DIS3L2 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Individuals suspected of having Perlman syndrome or individuals who have tested negative for other overgrowth syndromes. Family members may also be tested to determine carrier status of an identified variant in the DIS3L2 gene. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.


Official Gene Symbol OMIM ID
DIS3L2 614184
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Perlman Syndrome AR 267000

Related Test

Renal Cancer Panel


  • Alessandri J-L, Cuillier F, Ramful D, Ernould S, Robin S, Napoli-Cocci S de, Rivière J-P, Rossignol S. 2008. Perlman syndrome: Report, prenatal findings and review. American Journal of Medical Genetics Part A 146A: 2532–2537. PubMed ID: 18780370
  • Astuti D, Morris MR, Cooper WN, Staals RHJ, Wake NC, Fews GA, Gill H, Gentle D, Shuib S, Ricketts CJ, Cole T, Essen AJ van, van Lingen RA, Neri G, Opitz JM, Rump P, Stolte-Dijkstra I, Müller F, Pruijn GJ, Latif F, Maher ER. 2012. Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility. Nature Genetics 44: 277–284. PubMed ID: 22306653
  • Higashimoto K, Maeda T, Okada J, Ohtsuka Y, Sasaki K, Hirose A, Nomiyama M, Takayanagi T, Fukuzawa R, Yatsuki H, Koide K, Nishioka K, Joh K, Watanabe Y, Yoshiura K, Soejima H. 2013. Homozygous deletion of DIS3L2 exon 9 due to non-allelic homologous recombination between LINE-1s in a Japanese patient with Perlman syndrome. European Journal of Human Genetics 21: 1316–1319. PubMed ID: 23486540
  • Lubas M, Damgaard CK, Tomecki R, Cysewski D, Jensen TH, Dziembowski A. 2013. Exonuclease hDIS3L2 specifies an exosome-independent 3’-5’ degradation pathway of human cytoplasmic mRNA. EMBO J. 32: 1855–1868. PubMed ID: 23756462
  • Morris MR, Astuti D, Maher ER. 2013. Perlman Syndrome: Overgrowth, Wilms Tumor Predisposition and DIS3L2. American Journal of Medical Genetics Part C: Seminars in Medical Genetics 163: 106–113. PubMed ID: 23613427
  • Orphanet


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

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View Ordering Instructions

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2) Select Additional Test Options

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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