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Pontocerebellar Hypoplasia via the RARS2 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
7531 RARS2 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7531RARS281479 81479(x2) $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.

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

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

  • Renee Bend, PhD

Clinical Features and Genetics

Clinical Features

Pontocerebellar hypoplasias (PCH) are a group of clinically and genetically heterogeneous neurodegenerative disorders characterized by abnormal development of the pons, cerebellum and cerebral cortex; progressive microcephaly; psychomotor developmental delay; and swallowing difficulties (Rahman. 2012. PubMed ID: 22283595). Several subtypes have been described based on the clinical presentation, progression, and pathological and molecular defects. However, clinical overlapping features among various subtypes have been reported, and some genes have been implicated in more than one subtype, suggesting that PCH constitute a spectrum (Kastrissianakis. 2013. PubMed ID: 24047924; Ngoh. 2016. PubMed ID: 27061686).

PCH6 is distinguished by severe encephalopathy and elevated levels of lactate in the blood and cerebrospinal fluid. Additional features have been reported and include skeletal muscle respiratory chain defects, hypotonia, joint contractures, visual abnormalities, edema of the feet and hands, apnea, myoclonic seizures, and dysmorphic features. Symptoms are usually apparent at birth and death occurs in early infancy. PCH6 appears to be rare (Edvardson et al. 2007. PubMed ID: 17847012).

Genetics

All pontocerebellar hypoplasias are transmitted with an autosomal recessive mode of inheritance. PCH6 is caused by pathogenic variants in the RARS2 gene (Edvardson et al. 2007). About 20 pathogenic variants, mostly of the missense type, have been reported. Truncating pathogenic variants include six splice site variants and one variant that affects the initiation codon. One small causative deletion that is predicted to result in an in-frame deletion of one single amino acid has also been reported (Edvardson. 2007. PubMed ID: 17847012; Li. 2015. PubMed ID: 25809939; Human Gene Mutation Database).

Of note, one RARS2 splice site variant (c.110+5A>G) was reported in one patient with PCH who had elevated levels of lactate in the cerebrospinal fluid, which is characteristic of PCH6, and loss of motor neurons in the anterior horn of the spinal cord, which is characteristic of PCH1 (Edvardson et al. 2007. PubMed ID: 17847012).

The RARS2 gene encodes mitochondrial arginyl-transfer RNA (tRNA) synthetase, which is involved in the synthesis of all mitochondrial proteins (Edvardson. 2007. PubMed ID: 17847012).

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in the RARS2 gene appear to be a rare cause of pontocerebellar hypoplasia. To date, only 29 patients with such variants have been described worldwide (van Dijk et al. 2017. PubMed ID: 27683254).

Thus far, no gross deletions or duplications have been reported involving the RARS2 gene (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the RARS2 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with clinical features characteristic of PCH including severe encephalopathy, and elevated levels of lactate in the blood and cerebrospinal fluid with or without skeletal muscle respiratory chain defects; a family history consistent with autosomal recessive mode of inheritance; and family members of patients who have known RARS2 pathogenic variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in RARS2.

Gene

Official Gene Symbol OMIM ID
RARS2 611524
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Pontocerebellar Hypoplasia Type 6 AR 611523

Related Test

Name
Pontocerebellar Hypoplasia Panel

Citations

  • Edvardson et al. 2007. PubMed ID: 17847012
  • Human Gene Mutation Database (Bio-base).
  • Kastrissianakis et al. 2013. PubMed ID: 24047924
  • Li et al. 2015. PubMed ID: 25809939
  • Ngoh et al. 2016. PubMed ID: 27061686
  • Rahman. 2012. PubMed ID: 22283595
  • van Dijk et al. 2017. PubMed ID: 27683254

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

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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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