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
9851 DIS3L2 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9851DIS3L281479 81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

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.

Genetics

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).

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.

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.

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.

Gene

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

Disease

Name Inheritance OMIM ID
Perlman Syndrome AR 267000

Related Tests

Name
Cancer Panel
Renal Cancer Panel

Citations

  • 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/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.

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

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ORDER OPTIONS

View Ordering Instructions

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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.

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