Neuronal Ceroid Lipofuscinoses (Batten Disease) Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10311 ATP13A2 81479,81479 Order Options and Pricing
CLN3 81479,81479
CLN5 81479,81479
CLN6 81479,81479
CLN8 81479,81479
CTSD 81479,81479
CTSF 81479,81479
DNAJC5 81479,81479
GRN 81406,81479
KCTD7 81479,81479
MFSD8 81479,81479
PPT1 81479,81479
TPP1 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10311Genes x (13)81479 81406, 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

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.

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

The neuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative lysosomal storage disorders caused by the accumulation of autofluorescent material in various cell types, mainly cells of the cerebral cortex, cerebellar cortex, and retina (Dyken et al. 1988; Williams and Mole 2012; Bennett and Rakheja, 2013). 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 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; Vesa et al. 1995).

NCLs are clinically and genetically heterogeneous. A nomenclature based on the age of onset of symptoms and the disease-causing gene has been recently developed, which classifies NCLs into the following thirteen subtypes (Williams and Mole 2012):

Nomenclature

Current Previous Gene
CLN1 Haltia-Santavuori Disease PPT1
CLN2 Jansky-Bielschowsky Disease TPP1
CLN3 Batten Disease; Spielmeyer-Vogt Disease CLN3
CLN4 Parry Disease DNAJC5
CLN5 Finnish variant late infantile CLN5
CLN6 Lake-Cavanagh Disease (Juvenile and late infantile); Kufs Disease type A (Adult) CLN6
CLN7 Turkish variant late infantile MFSD8
CLN8 Northern epilepsy/EPMR CLN8
CLN10 Congenital CTSD
CLN11 NA GRN
CLN12 NA ATP13A2
CLN13 Kufs type B Disease CTSF
CLN14 NA KCTD7

The causative gene for the CLN9 phenotype has not yet been identified (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 mutations in CLN3.

Each subtye is further divided into subgroups based on the age of onset of symptoms. Subclassifications may be found in the individual gene test descriptions.

Genetics

Thirteen genes have been implicated in neuronal ceroid lipofuscinoses (NCLs): PPT1, TPP1, CLN3, CLN5, CLN6, MFSD8, CLN8, CTSD, DNAJC5, CTSF, ATP13A2, GRN, and KCTD7 (reviewed in Mole and Williams 2013).

Most NCLs are inherited in an autosomal recessive manner. Autosomal dominant inheritance is documented in several families with a clinical diagnosis of CLN4. Only a subset of these families have pathogenic variants in the DNAJC5 gene, suggesting genetic heterogeneity in the autosomal dominant form of the disease (Noskova et al. 2011).

Over 400 pathogenic variants have been reported in various ethnic and geographical populations such as Northern European, Chinese, Asian Indian, Hispanic, Pakistani, South American, Italian, Israeli, German, and Arabic. Pathogenic variants include missense; nonsense; splicing; small insertions or deletions, indels and large deletions (Human Gene Mutation Database).

The PPT1, TTP1, and CTSD genes encode lysosomal enzymes. The remaining ten genes encode transmembrane proteins that localize to the endoplasmic reticulum, the endosomal or lysosomal compartments. Although the functions of some of the encoded proteins remain unknown at this time, it has been speculated that all thirteen proteins are involved in neuroprotective pathways (Bennett and Rakheja 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

Molecular genetic testing of the neuronal ceroid lipofuscinoses: The percentage refers to the proportion of patients with various CLNs shown to have pathogenic variants in the corresponding genes. For CLN1, CLN2 and CLN10, patients included in the studies have deficient enzyme activities in the PPT1, TPP1, and CTSD enzymes, respectively. For the remaining subtypes, patients included in the studies met the diagnostic criteria of NCL (Mole and Williams 2013).

Disease Gene Percentage
CLN1 PPT1 >98%
CLN2 TPP1 97%
CLN3 CLN3 >98%
CLN4 DNAJC5 >95%
CLN5 CLN5 90-95%
CLN6 CLN6 92%
CLN7 MFSD8 >95%
CLN8 CLN8 90-95%
CLN10 CTSD ~95%
CLN11 GRN ~95%
CLN12 ATP13A2 ~95%
CLN13 CTSF ~95%
CLN14 KCTD7 ~95%

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes 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 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 this NGS NCL panel are patients with clinical features suggestive of neuronal ceroid lipofuscinosis regardless of the age of onset of symptoms and mode of inheritance of the disease.

Genes

Official Gene Symbol OMIM ID
ATP13A2 610513
CLN3 607042
CLN5 608102
CLN6 606725
CLN8 607837
CTSD 116840
CTSF 603539
DNAJC5 611203
GRN 138945
KCTD7 611725
MFSD8 611124
PPT1 600722
TPP1 607998
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Bennett MJ, Rakheja D. 2013. The neuronal ceroid-lipofuscinoses: The Neuronal Ceroid-Lipofuscinoses. Developmental Disabilities Research Reviews 17: 254–259. PubMed ID: 23798013
  • Dyken PR, Opitz JM, Reynolds JF, Pullarkat RK. 1988. Reconsideration of the classification of the neuronal ceroid-lipofuscinoses. American Journal of Medical Genetics 31: 69–84. PubMed ID: 3146331
  • Human Gene Mutation Database (Bio-base).
  • 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
  • Nosková L, Stránecký V, Hartmannová H, Pristoupilová A, Barešová V, Ivánek R, Hulková H, Jahnová H, Zee J van der, Staropoli JF, Sims KB, Tyynelä J, Van Broeckhoven C, Nijssen PC, Mole SE, Elleder M, Kmoch S. 2011. Mutations in DNAJC5, Encoding Cysteine-String Protein Alpha, Cause Autosomal-Dominant Adult-Onset Neuronal Ceroid Lipofuscinosis. The American Journal of Human Genetics 89: 241–252. PubMed ID: 21820099
  • Rider JA and Rider DL 1988. Batten disease: past, present, and future. Am J Med Genet Suppl 5:21-6. PubMed ID: 3146319
  • Schulz A. et al. 2004. Annals of neurology. 56: 342-50. PubMed ID: 15349861
  • Vesa J, Hellsten E, Verkruyse LA, Camp LA, Rapola J, Santavuori P, Hofmann SL, Peltonen L. 1995. Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. Nature 376:584-587. PubMed ID: 7637805
  • Williams RE and Mole SE 2012. New nomenclature and classification scheme for the neuronal ceroid lipofuscinoses. 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.

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

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

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