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Neuronal Ceroid Lipofuscinosis 12 via the ATP13A2 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
11097 ATP13A2 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11097ATP13A281479 81479,81479 $990 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.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Renee Bend, PhD

Clinical Features and Genetics

Clinical Features

The neuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative lysosomal storage disorders caused by the accumulation of ceroid and lipofuscin in various cell types, mainly cells of the cerebral cortex, cerebellar cortex, and retina (Dyken et al. 1988; Williams and Mole 2012). Characteristic features at onset include clumsiness; deterioration of vision and psychomotor functions; seizures and behavioral changes. Progression of clinical features results ultimately in total disability, blindness and premature death. Although NCL affects primarily children, age of onset of symptoms varies from infancy to adulthood. The incidence of NCL is variable and ranges from 1.3 to 7 per 100,000 (Mole and Williams 2013). However, it is more common in northern European populations, particularly Finland where the incidence may reach 1 in 12,500 individuals and a carrier frequency of 1 in 70 (Rider and Rider 1988). NCLs are clinically and genetically heterogeneous. A nomenclature and classification based both on the age of onset of symptoms and the disease-causing gene has been recently developed, which classifies NCLs into thirteen subtypes (CLN1-8, 10-14) (Williams and Mole 2012). The causative gene for the CLN9 phenotype has not been identified yet (Schulz et al. 2004).

Of note, NCLs were previously known as Batten disease. However, in recent nomenclature, Batten disease only applies to NCL caused by pathogenic variants in CLN3.

CLN12 is characterized by juvenile onset and slow progression. To date, one single family with four affected individuals has been documented in the literature. Symptoms started around the age of 8 years with learning difficulties. As the disease progressed additional symptoms appeared and included bradykinesia, limb stiffness, gait disturbances, dysarthria, clumsiness, spasticity, myotonic jerks, seizures, slow eye movements, and peripheral neuropathy. MRI findings indicated brain atrophy. In this family, the diagnosis of neuronal ceroid lipofuscinosis was confirmed by the presence of lipofuscin deposits in post-mortem pathological studies of the brain and retina (De Volder et al. 1990; Bras et al. 2012).

Genetics

Most CLNs, including CLN12, are inherited in an autosomal recessive manner. Thirteen genes have been implicated in the disorder: PPT1, TPP1, CLN3, CLN5, CLN6, MFSD8, CLN8, CTSD, DNAJC5, CTSF, ATP13A2, GRN, and KCTD7 (Mole and Williams 2013).

CLN12 is caused by pathogenic variants in the ATP13A2 gene. A homozygous missense variant, c.2429T>G (p.Met810Arg), was found in the one reported family (Bras et al. 2012; De Volder et al. 1990). Support for the pathogenicity of this variant include its segregation with the disease in the described family; and its absence from control populations in various databases. Importantly, a homozygous truncating variant, c.1620delG, in the ATP13A2 gene was previously reported in a dog model of late onset lethal form of NCL. This variant causes exon skipping as the result of a broken exonic splicing enhancer motif (Wöhlke et al. 2011; Farias et al. 2011).

The ATP13A2 gene encodes a lysosomal transport protein that is part of the P-type superfamily of ATPases (Schultheis et al. 2004).

Pathogenic variants in ATP13A2 appear to be a rare cause of NCL. Only one NCL family with such variants has been reported to date (Bras et al. 2012).

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in ATP13A2 appear to be a rare cause of NCL. Only one NCL family with a pathogenic ATP13A2 variant has been reported to date (Bras et al. 2012).

Testing Strategy

This test provides full coverage of all coding exons of the ATP13A2 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 the ATP13A2 test are patients with a clinical diagnosis suggestive of neuronal ceroid lipofuscinosis and no pathogenic variants in the remaining NCL genes. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ATP13A2.

Gene

Official Gene Symbol OMIM ID
ATP13A2 610513
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Ceroid Lipofuscinosis Neuronal 12 AR 606693

Citations

  • Bras J et al. 2012. Human molecular genetics. 21: 2646-50 PubMed ID: 22388936
  • De Volder AG. et al. 1990. Journal of neurology, neurosurgery, and psychiatry. 53: 1063-7 PubMed ID: 2292699
  • Dyken P.R. 1988. American journal of medical genetics. Supplement. 5: 69-84. PubMed ID: 3146331
  • Farias FH et al. Neurobiol Dis. 2011 Jun;42(3):468-74. PubMed ID: 21362476
  • Mole S.E., Williams R.E. 2013. Neuronal Ceroid-Lipofuscinoses. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301601
  • Rider J.A., Rider D.L. 1988. American journal of medical genetics. Supplement. 5: 21-6. PubMed ID: 3146319
  • Schultheis PJ., Hagen TT. 2004. Biochemical and biophysical research communications. 323: 731-8. PubMed ID: 15381061
  • Schulz A. et al. 2004. Annals of neurology. 56: 342-50. PubMed ID: 15349861
  • Wöhlke A. et al. 2011. PLoS genetics. 7: e1002304. PubMed ID: 22022275
  • Williams R.E., Mole S.E. 2012. Neurology. 79: 183-91. PubMed ID: 22778232

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

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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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.
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