Aceruloplasminemia via the CP 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
8039 CP 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8039CP81479 81479 $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.

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

For Reflex to PGxome pricing click here.

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 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

Clinical Features

Aceruloplasminemia is an iron accumulation disorder resulting in retinal degeneration, diabetes mellitus and neurological disease. Symptom onset occurs between ages 25 and 60 with individuals initially presenting with anemia. Neurologic findings include ataxia and muscle movement impairment including grimacing, blepharospasm, tremors, chorea, and facial/neck dystonia (Kono 2012; Miyajima 2003). Genetic testing is helpful in the differential diagnosis of Aceruloplasminemia from other neurodegeneration with brain iron accumulation (NBIA) disorders including neuroferritinopathy, PLA2G6-associated neurodegeneration as well as copper metabolic disorders (Wilson and Menkes disease), Huntington’s disease, dystonia, and Parkinson’s disease. Treatments for Aceruloplasminemia include iron chelating agents, fresh frozen plasma containing ceruloplasmin, and antioxidants (Miyajima 2003).

Genetics

Aceruloplasminemia is inherited in an autosomal recessive manner through pathogenic variants in the CP gene. Missense mutations leading to impaired secretion, copper incorporation, and enzymatic activity occur throughout the coding region and represent about half of the reported causative variants in the CP gene (Hellman et al. 2002; Hellman et al. 2002). Frameshift, splice site and nonsense variants represent ~30%, 15% and 15% of cases respectively (Kono 2012). No clear genotype-phenotype correlations exist for Aceruloplasminemia (Miyajima 2003).

The CP gene encodes the ceruloplasmin enzyme that is expressed both as a soluble serum and membrane bound protein through alternative splicing and omission of exon 19. Serum ceruloplasmin is involved in iron homeostasis and plays a role in mobilization of iron from tissue stores and transportation across the basolateral surface of enterocytes. Membrane bound ceruloplasmin is present in astrocytes and is thought to serve as an antioxidant in the central nervous system (Kono 2012; Miyajima 2015).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity is problematic as absence of serum ceruloplasmin is mirrored in other disorders including Wilson’s disease. To date, large ceruloplasminemia patient cohort studies have not been performed to assess clinical sensitivity of CP genetic testing. Therefore, clinical sensitivity of this test is currently unknown. Analytical sensitivity should be high because all pathogenic variants reported are detected by this method.

Testing Strategy

This test provides full coverage of all coding exons of the CP 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for testing have an absence of serum ceruloplasmin, low copper (less than 10µg/dL) and iron (less than 45µg/dL) serum concentration, elevated serum ferritin (850-4000 ng/mL), and increased hepatic iron concentration. MRI scans displaying iron accumulation in the brain are also indicative of disease. Ideal candidates also present with diabetes mellitus, retinal degeneration, anemia, and neurologic disease (Kono 2012). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CP.

Gene

Official Gene Symbol OMIM ID
CP 117700
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Aceruloplasminemia AR 604290

Related Test

Name
Menkes Disease and Hereditary Motor Neuropathy via the ATP7A Gene

Citations

  • Hellman NE. et al. 2002. The Journal of biological chemistry. 277: 1375-80. PubMed ID: 11689569
  • Hellman NE. et al. 2002. The Journal of biological chemistry. 277: 46632-8. PubMed ID: 12351628
  • Kono S. 2012. Current drug targets. 13: 1190-9.  PubMed ID: 22515741
  • Miyajima H. 2015. Neuropathology : official journal of the Japanese Society of Neuropathology. 35: 83-90. PubMed ID: 25168455
  • Miyajima. 2013. Ceruloplasminemia. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301666

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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