Pontocerebellar Hypoplasia via the CLP1 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
10457 CLP1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
10457CLP181479 81479(x2) $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

  • 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 (Barth. 1993. PubMed ID: 8147499; Namavar et al. 2011. PubMed ID: 21368912). 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 (Burglen et al. 2012. PubMed ID: 22452838; Samanta and Willis. 2016. PubMed ID: 27570394).

A new form of PCH, proposed to be designated PCH10, is characterized by delayed or absent developmental milestones, intellectual disability, seizures, spasticity, hypertonia, and increased deep tendon reflexes. Additional features include irritability, jitteriness, hypotonia, and visual impairment in the form of primary optic atrophy or strabismus. Facial features include high arched eyebrows, prominent eyes, long palpebral fissures and eyelashes. Electromyography findings include age-dependent muscle fibrillations and high amplitude motor unit potentials, indicating progressive loss of spinal motor neurons. Electrophysiological studies indicate axonal sensorimotor neuropathies (Schaffer et al. 2014. PubMed ID: 24766810; Karaca et al. 2014. PubMed ID: 24766809).

Genetics

All pontocerebellar hypoplasias are transmitted with an autosomal recessive mode of inheritance. A homozygous missense variant, Arg140His, in the CLP1 gene has been reported to be the cause of PCH10 in all affected members of 9 consanguineous families with history of the disease. Evidence for pathogenicity of the missense variant include in vitro functional studies, which revealed a defective kinase activity of the CLP1 mutant enzyme and destabilization of the tRNA endonuclease complex (TSEN). Animal model studies confirmed the pathogenicity of this variant (Schaffer et al. 2014. PubMed ID: 24766810; Karaca et al. 2014. PubMed ID: 24766809).

CLP1 encodes an RNA kinase. It is involved in tRNA splicing via its interaction with the TSEN complex (Weitzer and Martinez. 2007. PubMed ID: 17786051). The R140H variant is postulated to cause impaired splicing, as the result of decreased interactions between mutant CLP1 and the TSEN complex (Hanada et al. 2013. PubMed ID: 23474986; Karaca et al. 2014. PubMed ID: 24766809).

Clinical Sensitivity - Sequencing with CNV PGxome

To date, one pathogenic missense variant has been reported to be the cause of PCH10 in 9, apparently unrelated, consanguineous families from the Middle East (Schaffer et al. 2014. PubMed ID: 24766810; Karaca et al. 2014. PubMed ID: 24766809).

Testing Strategy

This test provides full coverage of all coding exons of the CLP1 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 pontocerebellar hypoplasia and a family history consistent with autosomal recessive mode of inheritance. Family members of patients who have known CLP1 pathogenic variants are also candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CLP1.

Gene

Official Gene Symbol OMIM ID
CLP1 608757
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Pontocerebellar Hypoplasia Type 10 AR 615803

Related Tests

Name
AMPD2-Related Disorders via the AMPD2 Gene
Pontocerebellar Hypoplasia via the SEPSECS Gene

Citations

  • Barth. 1993. PubMed ID: 8147499
  • Burglen et al. 2012. PubMed ID: 22452838
  • Hanada et al. 2013. PubMed ID: 23474986
  • Karaca et al. 2014. PubMed ID: 24766809
  • Namavar et al. 2011. PubMed ID: 21368912
  • Samanta and Willis. 2016. PubMed ID: 27570394
  • Schaffer et al. 2014. PubMed ID: 24766810
  • Weitzer and Martinez. 2007. PubMed ID: 17786051

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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