Neuronal Ceroid Lipofuscinosis 2 via the TPP1 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
7203 TPP1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7203TPP181479 81479 $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 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 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 the 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 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 mutations in CLN3.

CLN2, also known as Jansky-Bielschowsky disease is further divided into two subgroups based on the age of onset of symptoms.

1) CLN2 disease, late infantile, is the most prevalent of the two. It is characterized by onset between 2-4 years of age and death in the early teens. Epileptic seizures are the presenting symptoms in most cases. They are followed by ataxia, vision impairment and psychomotor deterioration (Sleat et al. 1999).

2) CLN2 disease, juvenile, is characterized by onset between 6-10 years, progressive cognitive and motor dysfunction and milder phenotype compared to the late infantile form (Bessa et al. 2008).

Genetics

Most CLNs 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). Both forms of CLN2 are caused by pathogenic variants in the TPP1 gene (Sleat et al. 1997). Over 100 pathogenic variants have been reported in various ethnic populations, and include missense; nonsense; splicing; small insertions or deletions; and indels. Only one large pathogenic deletion was reported to date (Mole et al. 1999).

The TPP1 gene encodes tripeptidyl peptidase 1 (TPP1), a lysosomal enzyme that is involved in the cleavage of tripeptides from small proteins undergoing degradation in the lysosomes.

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in TPP1 were detected in ~ 95% of patients with NCL and TPP1 enzyme deficiency (Sleat et al. 1999).

Testing Strategy

This test provides full coverage of all coding exons of the TPP1 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 a clinical diagnosis of NCL and deficient TPP1 enzyme activity. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in TPP1.

Gene

Official Gene Symbol OMIM ID
TPP1 607998
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Ceroid Lipofuscinosis Neuronal 2 AR 204500

Related Test

Name
Neuronal Ceroid Lipofuscinoses (Batten Disease) Panel

Citations

  • Bessa C, Teixeira CA, Dias A, Alves M, Rocha S, Lacerda L, Loureiro L, Guimarães A, Ribeiro MG. 2008. CLN2/TPP1 deficiency: the novel mutation IVS7-10A>G causes intron retention and is associated with a mild disease phenotype. Mol. Genet. Metab. 93: 66–73. PubMed ID: 17959406
  • 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
  • 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
  • Mole SE, Mitchison HM, Munroe PB. 1999. Molecular basis of the neuronal ceroid lipofuscinoses: mutations in CLN1, CLN2, CLN3, and CLN5. Hum Mutat. 14:199-215. PubMed ID: 10477428
  • Rider J.A., Rider D.L. 1988. American journal of medical genetics. Supplement. 5: 21-6. PubMed ID: 3146319
  • Schulz A. et al. 2004. Annals of neurology. 56: 342-50. PubMed ID: 15349861
  • Sleat DE, Donnelly RJ, Lackland H, Liu CG, Sohar I, Pullarkat RK, Lobel P. 1997. Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis. Science 277: 1802–1805. PubMed ID: 9295267
  • Sleat DE, Gin RM, Sohar I, Wisniewski K, Sklower-Brooks S, Pullarkat RK, Palmer DN, Lerner TJ, Boustany R-M, Uldall P. 1999. Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder. The American Journal of Human Genetics 64: 1511–1523. PubMed ID: 10330339
  • 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 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.

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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