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 Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 7203 | TPP1 | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
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.
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.
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, Guimarăes 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.
- 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
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