Neuronal Ceroid-Lipofuscinoses Panel
GTR Test Accession: Help GTR000506325.5
CAP
INHERITED DISEASEMETABOLIC DISEASENERVOUS SYSTEM ... View more
Last updated in GTR: 2021-01-19
Last annual review date for the lab: 2023-07-18 LinkOut
At a Glance
Diagnosis; Monitoring; Mutation Confirmation; ...
Neuronal ceroid lipofuscinosis 2; Ceroid lipofuscinosis, neuronal, 4 (Kufs type); Ceroid lipofuscinosis, neuronal, 6A; ...
ATP13A2 (1p36.13), CLN3 (16p12.1), CLN5 (13q22.3), CLN6 (15q23), CLN8 (8p23.3), ...
Molecular Genetics - Deletion/duplication analysis: Next-Generation (NGS)/Massively parallel sequencing (MPS); ...
The target population for this test is patients suspected of …
Mutations in CLN3 are the main cause of classic juvenile …
Establish or confirm diagnosis
Ordering Information
Offered by: Help
Specimen Source: Help
Who can order: Help
  • Genetic Counselor
  • Health Care Provider
  • Licensed Physician
  • Nurse Practitioner
  • Physician Assistant
  • Registered Nurse
CPT codes: Help
**AMA CPT codes notice
Contact Policy: Help
Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.
How to Order: Help
All samples should be shipped via overnight delivery at room temperature.
No weekend or holiday deliveries.
Label each specimen with the patient’s name, date of birth and date sample collected.
Send specimens with complete requisition and consent form, otherwise, specimen processing may be delayed.
Order URL
Test service: Help
Clinical Testing/Confirmation of Mutations Identified Previously
Confirmation of research findings
Test additional service: Help
Custom Prenatal Testing
Custom mutation-specific/Carrier testing
Test development: Help
Test developed by laboratory (no manufacturer test name)
Informed consent required: Help
No
Pre-test genetic counseling required: Help
Decline to answer
Post-test genetic counseling required: Help
Decline to answer
Recommended fields not provided:
Conditions Help
Total conditions: 11
Condition/Phenotype Identifier
Test Targets
Genes Help
Total genes: 13
Gene Associated Condition Germline or Somatic Allele (Lab-provided) Variant in NCBI
Methodology
Total methods: 2
Method Category Help
Test method Help
Instrument *
Deletion/duplication analysis
Next-Generation (NGS)/Massively parallel sequencing (MPS)
Sequence analysis of the entire coding region
Next-Generation (NGS)/Massively parallel sequencing (MPS)
* Instrument: Not provided
Clinical Information
Test purpose: Help
Diagnosis; Monitoring; Mutation Confirmation; Pre-symptomatic; Risk Assessment; Screening
Clinical validity: Help
Mutations in CLN3 are the main cause of classic juvenile NCL. The first symptom is typically insidious onset of retinitis pigmentosa at age 4-6 years, followed by progressive cognitive decline and seizures. Other symptoms may include myoclonus, parkinsonism, severe dysarthria and behavioral issues with angry outbursts and physical violence. CLN3 … View more
View citations (11)
  • Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder. Sleat DE, et al. Am J Hum Genet. 1999;64(6):1511-23. doi:10.1086/302427. PMID: 10330339.
  • Palmitoyl protein thioesterase (PPT) localizes into synaptosomes and synaptic vesicles in neurons: implications for infantile neuronal ceroid lipofuscinosis (INCL). Lehtovirta M, et al. Hum Mol Genet. 2001;10(1):69-75. doi:10.1093/hmg/10.1.69. PMID: 11136716.
  • Lysosomal localization of the neuronal ceroid lipofuscinosis CLN5 protein. Isosomppi J, et al. Hum Mol Genet. 2002;11(8):885-91. doi:10.1093/hmg/11.8.885. PMID: 11971870.
  • Neurology of the neuronal ceroid-lipofuscinoses: late infantile and juvenile types. Boustany RM, et al. Am J Med Genet. 1992;42(4):533-5. doi:10.1002/ajmg.1320420421. PMID: 1609833.
  • The spectrum of Jansky-Bielschowsky disease. Santavuori P, et al. Neuropediatrics. 1991;22(2):92-6. doi:10.1055/s-2008-1071423. PMID: 1649978.
  • Chang JW, Choi H, Kim HJ, Jo DG, Jeon YJ, Noh JY, Park WJ, Jung YK. Neuronal vulnerability of CLN3 deletion to calcium-induced cytotoxicity is mediated by calsenilin. Hum Mol Genet. 2007;16(3):317-26. doi:10.1093/hmg/ddl466. Epub 2006 Dec 22. PMID: 17189291.
  • Siintola E, Topcu M, Aula N, Lohi H, Minassian BA, Paterson AD, Liu XQ, Wilson C, Lahtinen U, Anttonen AK, Lehesjoki AE. The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative lysosomal transporter. Am J Hum Genet. 2007;81(1):136-46. doi:10.1086/518902. Epub 2007 May 14. PMID: 17564970.
  • Fritchie K, Siintola E, Armao D, Lehesjoki AE, Marino T, Powell C, Tennison M, Booker JM, Koch S, Partanen S, Suzuki K, Tyynelä J, Thorne LB. Novel mutation and the first prenatal screening of cathepsin D deficiency (CLN10). Acta Neuropathol. 2009;117(2):201-8. doi:10.1007/s00401-008-0426-7. Epub 2008 Sep 02. PMID: 18762956.
  • A novel CLN8 mutation in late-infantile-onset neuronal ceroid lipofuscinosis (LINCL) reveals aspects of CLN8 neurobiological function. Vantaggiato C, et al. Hum Mutat. 2009;30(7):1104-16. doi:10.1002/humu.21012. PMID: 19431184.
  • Kielar C, Wishart TM, Palmer A, Dihanich S, Wong AM, Macauley SL, Chan CH, Sands MS, Pearce DA, Cooper JD, Gillingwater TH. Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease. Hum Mol Genet. 2009;18(21):4066-80. doi:10.1093/hmg/ddp355. Epub 2009 Jul 29. PMID: 19640925.
  • Mole, S., Neuronal Ceroid-Lipofuscinoses. 2001 Oct 10 [Updated 2010 Mar 2], GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013.
Clinical utility: Help
Establish or confirm diagnosis
View citations (11)
  • Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder. Sleat DE, et al. Am J Hum Genet. 1999;64(6):1511-23. doi:10.1086/302427. PMID: 10330339.
  • Palmitoyl protein thioesterase (PPT) localizes into synaptosomes and synaptic vesicles in neurons: implications for infantile neuronal ceroid lipofuscinosis (INCL). Lehtovirta M, et al. Hum Mol Genet. 2001;10(1):69-75. doi:10.1093/hmg/10.1.69. PMID: 11136716.
  • Lysosomal localization of the neuronal ceroid lipofuscinosis CLN5 protein. Isosomppi J, et al. Hum Mol Genet. 2002;11(8):885-91. doi:10.1093/hmg/11.8.885. PMID: 11971870.
  • Neurology of the neuronal ceroid-lipofuscinoses: late infantile and juvenile types. Boustany RM, et al. Am J Med Genet. 1992;42(4):533-5. doi:10.1002/ajmg.1320420421. PMID: 1609833.
  • The spectrum of Jansky-Bielschowsky disease. Santavuori P, et al. Neuropediatrics. 1991;22(2):92-6. doi:10.1055/s-2008-1071423. PMID: 1649978.
  • Chang JW, Choi H, Kim HJ, Jo DG, Jeon YJ, Noh JY, Park WJ, Jung YK. Neuronal vulnerability of CLN3 deletion to calcium-induced cytotoxicity is mediated by calsenilin. Hum Mol Genet. 2007;16(3):317-26. doi:10.1093/hmg/ddl466. Epub 2006 Dec 22. PMID: 17189291.
  • Siintola E, Topcu M, Aula N, Lohi H, Minassian BA, Paterson AD, Liu XQ, Wilson C, Lahtinen U, Anttonen AK, Lehesjoki AE. The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative lysosomal transporter. Am J Hum Genet. 2007;81(1):136-46. doi:10.1086/518902. Epub 2007 May 14. PMID: 17564970.
  • Fritchie K, Siintola E, Armao D, Lehesjoki AE, Marino T, Powell C, Tennison M, Booker JM, Koch S, Partanen S, Suzuki K, Tyynelä J, Thorne LB. Novel mutation and the first prenatal screening of cathepsin D deficiency (CLN10). Acta Neuropathol. 2009;117(2):201-8. doi:10.1007/s00401-008-0426-7. Epub 2008 Sep 02. PMID: 18762956.
  • A novel CLN8 mutation in late-infantile-onset neuronal ceroid lipofuscinosis (LINCL) reveals aspects of CLN8 neurobiological function. Vantaggiato C, et al. Hum Mutat. 2009;30(7):1104-16. doi:10.1002/humu.21012. PMID: 19431184.
  • Kielar C, Wishart TM, Palmer A, Dihanich S, Wong AM, Macauley SL, Chan CH, Sands MS, Pearce DA, Cooper JD, Gillingwater TH. Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease. Hum Mol Genet. 2009;18(21):4066-80. doi:10.1093/hmg/ddp355. Epub 2009 Jul 29. PMID: 19640925.
  • Mole, S., Neuronal Ceroid-Lipofuscinoses. 2001 Oct 10 [Updated 2010 Mar 2], GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013.

Target population: Help
The target population for this test is patients suspected of having a diagnosis of Neuronal Ceroid-Lipofuscinoses.
Variant Interpretation:
What is the protocol for interpreting a variation as a VUS? Help
Variants are identified and evaluated using a custom collection of bioinformatic tools and comprehensively interpreted by our team of directors and genetic counselors.

Will the lab re-contact the ordering physician if variant interpretation changes? Help
Yes.
Research:
Is research allowed on the sample after clinical testing is complete? Help
http://dnatesting.uchicago.edu/research-consent-form
Recommended fields not provided:
Technical Information
Availability: Help
Tests performed
Entire test performed in-house
Analytical Validity: Help
Analytical Sensitivity 99-100% Accuracy 100% Precision 100%
Assay limitations: Help
This assay covers the coding and immediate flanking regions of the included genes. Variants in the promoter region and in other non-coding regions will not be detected. Variants that occur within regions of high homology and/or repetitiveness may not be detected due to issues with alignment. The technical sensitivity of … View more
Proficiency testing (PT):
Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Formal PT program

PT Provider: Help
American College of Medical Genetics / College of American Pathologists, ACMG/CAP
VUS:
Software used to interpret novel variations Help
A custom collection of bioinformatics tools

Laboratory's policy on reporting novel variations Help
The laboratory reports novel variations.
Recommended fields not provided:
Regulatory Approval
FDA Review: Help
Category: FDA exercises enforcement discretion
Additional Information

IMPORTANT NOTE: NIH does not independently verify information submitted to GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.