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Neuronal Ceroid Lipofuscinosis 8 via the CLN8 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
CLN8 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7603CLN881479 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.


Genetic Counselors


  • 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 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. CLN8 is further divided into two subgroups based on the age of onset, disease course, and severity of symptoms.

1-CLN8 disease, late infantile variant, is characterized by onset between 2-7 years of age and rapid course. Symptoms at onset include speech delay, ataxia, seizures, myoclonus, and visual and psychomotor decline. Most patients are wheelchair-bound within a few years of disease onset (Ranta et al. 2004; Topcu et al. 2004). This form of NCL was designated as Turkish variant late infantile NCL because it was first described in Turkish patients (Mitchell et al. 2001).

2-CLN8 disease, EPMR (Progressive Epilepsy with Mental Retardation), also known as Northern epilepsy, is characterized by onset between 5-10 years of age and survival prolonged into the fifth decade of life. Epilepsy, marked by tonic-clonic seizures that are resistant to drugs, is the first symptom, followed by mental retardation. Additional features include behavioral changes, mainly during puberty; loss of control of fine motor skills, and balance difficulties. Visual impairment was reported in some cases. The disease course is usually less severe than that of the late infantile variant. The vast majority of patients affected with EPMR are from Northern Finland (Hirvasniemi et al. 1994; Ranta and Lehesjoki, 2000).


Most CLNs are inherited in an autosomal recessive manner. Both forms of CLN8 are caused by pathogenic variants in the CLN8 gene and are autosomal recessive.

A CLN8- founder mutation, (c.70C>G; p.Arg24Gly), with a carrier frequency of 1:135 was documented to be the cause of EPMR in patients from Finland (Ranta et al. 1999; Ranta et al. 2000).

CLN8 disease, late infantile variant, is caused by other pathogenic variants in CLN8, which were first documented in Turkish families (Ranta et al. 2004). More recent data indicate that this from of NCL is pan-ethnic. About 25 CLN8 pathogenic variants, mainly of the missense type, have been reported. A few small deletions, two of which are in-frame; and a large deletion have also been reported. CLN8 pathogenic variants were documented in patients from diverse ethnic and geographic origins such as Italy, Israel, Germany, and Pakistan (Cannelli et al. 2006; Zelnik et al. 2007; Reinhardt et al. 2010).

The CLN8 gene encodes a transmembrane protein which is hypothesized to be involved in cell survival (Vantaggiato et al. 2009).

Clinical Sensitivity - Sequencing with CNV PG-Select

This test will detect pathogenic variants in the CLN8 gene in up to 95% of patients, with clinical diagnosis of CLN8 disease, late infantile variant, of various ethnicity; and in nearly all patients with EPMR (Mole and Williams 2013).

Testing Strategy

This test provides full coverage of all coding exons of the CLN8 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 CLN8 disease, variant late infantile, regardless of their ethnic or geographical origins; and patients with EPMR. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CLN8.


Official Gene Symbol OMIM ID
CLN8 607837
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Neuronal Ceroid Lipofuscinoses (Batten Disease) Panel


  • Cannelli N, Cassandrini D, Bertini E, Striano P, Fusco L, Gaggero R, Specchio N, Biancheri R, Vigevano F, Bruno C, Simonati A, Zara F, Santorelli FM. 2006. Novel mutations in CLN8 in Italian variant late infantile neuronal ceroid lipofuscinosis: Another genetic hit in the Mediterranean. Neurogenetics 7:111-117. PubMed ID: 16570191
  • 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
  • Hirvasniemi A, Lang H, Lehesjoki AE, Leisti J. 1994. Northern epilepsy syndrome: an inherited childhood onset epilepsy with associated mental deterioration. J Med Genet 31:177-182. PubMed ID: 8014963
  • Mitchell WA, Wheeler RB, Sharp JD, Bate SL, Gardiner RM, Ranta US, Lonka L, Williams RE, Lehesjoki AE, Mole SE. 2001. Turkish variant late infantile neuronal ceroid lipofuscinosis (CLN7) may be allelic to CLN8. Eur J Paediatr Neurol 5 Suppl A:21-27. PubMed ID: 11589000
  • 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
  • Ranta S, Lehesjoki AE. 2000. Northern epilepsy, a new member of the NCL family. Neurol Sci 21(3 Suppl):S43-7. Review. PubMed ID: 11073227
  • Ranta S, Topcu M, Tegelberg S, Tan H, Ustübütün A, Saatci I, Dufke A, Enders H, Pohl K, Alembik Y, Mitchell WA, Mole SE, Lehesjoki AE. 2004. Variant late infantile neuronal ceroid lipofuscinosis in a subset of Turkish patients is allelic to Northern epilepsy. Hum Mutat 23:300-305. PubMed ID: 15024724
  • Ranta S, Zhang Y, Ross B, Lonka L, Takkunen E, Messer A, Sharp J, Wheeler R, Kusumi K, Mole S, Liu W, Soares MB, Bonaldo MF, Hirvasniemi A, de la Chapelle A, Gilliam TC, Lehesjoki AE. 1999. The neuronal ceroid lipofuscinoses in human EPMR and mnd mutant mice are associated with mutations in CLN8. Nat Genet. 23:233-236. PubMed ID: 10508524
  • Reinhardt K, Grapp M, Schlachter K, Brück W, Gärtner J, Steinfeld R. 2010. Novel CLN8 mutations confirm the clinical and ethnic diversity of late infantile neuronal ceroid lipofuscinosis. Clin Genet 77:79-85. PubMed ID: 19807737
  • 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
  • Topçu M, Tan H, Yalnizo?lu D, Usubütün A, Saatçi I, Aynaci M, Anlar B, Topalo?lu H, Turanli G, Köse G, Aysun S. 2004. Evaluation of 36 patients from Turkey with neuronal ceroid lipofuscinosis: clinical, neurophysiological, neuroradiological and histopathologic studies.. Turk J Pediatr. 46:1-10. PubMed ID: 15074367
  • Vantaggiato C, Redaelli F, Falcone S, Perrotta C, Tonelli A, Bondioni S, Morbin M, Riva D, Saletti V, Bonaglia MC, Giorda R, Bresolin N, Clementi E, Bassi MT. 2009. A novel CLN8 mutation in late-infantile-onset neuronal ceroid lipofuscinosis (LINCL) reveals aspects of CLN8 neurobiological function. Hum Mutat. 30:1104-1116. PubMed ID: 19431184
  • 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
  • Zelnik N, Mahajna M, Iancu TC, Sharony R, Zeigler M. 2007. A novel mutation of the CLN8 gene: is there a Mediterranean phenotype? Pediatr Neurol. 36:411-413. PubMed ID: 17560505


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.

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