Neuronal Ceroid Lipofuscinosis 4 via the DNAJC5 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
4135 DNAJC5 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4135DNAJC581479 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 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 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). 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 pathogenic variants in CLN3.

CLN4 is characterized by an autosomal dominant mode of inheritance, adult onset, rapid progression, and reduced life span. Symptoms start usually between the third and fourth decades of life with tonic-clonic seizures. Additional symptoms appear with the progression of the disease and include myoclonic seizures, dementia, attention deficit, memory loss, speech abnormality, tremor, voluntary movement disturbance and parkinsonian features (Burneo et al. 2003). MRI findings are consistent with cerebral and cerebellar brain atrophy. Vision is spared (Nosková et al. 2011).

Genetics

CLN4 is the only neuronal ceroid lipofuscinosis that is inherited with an autosomal dominant manner. The penetrance is high. It is caused by pathogenic variants in the DNAJC5 gene. To date, only two variants have been implicated in the disorder. A missense variant (c.344T>G, p.Leu115Arg) and a three-nucleotide deletion that is predicted to result in the in-frame deletion of an adjacent residue (p.Leu116del) have been reported in a total of 8 unrelated families (Nosková et al. 2011; Benitez et al. 2011; Greaves et al. 2012; Velinov et al. 2012). These two variants accounted for about 38% of cases with unexplained adult-onset. Haplotype analyses indicate that both variants are recurrent (Cadieux-Dion et al. 2013).

The DNAJC5 gene encodes cysteine-string protein alpha (CSPalpha), which is postulated to play a neuroprotective role. DNAJC5 pathogenic variants result in synaptic dysfunction and reduced life span in mice (Schmitz F. et al. 2006).

Clinical Sensitivity - Sequencing with CNV PG-Select

The two pathogenic variants in the DNAJC5 gene accounted for about 38% of cases with unexplained adult-onset (Cadieux-Dion et al. 2013).

Testing Strategy

This test provides full coverage of all coding exons of the DNAJC5 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for the DNAJC5 test are patients with a clinical diagnosis suggestive of neuronal ceroid lipofuscinosis and autosomal dominant inheritance.

Gene

Official Gene Symbol OMIM ID
DNAJC5 611203
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Ceroid Lipofuscinosis Neuronal 4B Autosomal Dominant AD 162350

Related Tests

Name
Neuronal Ceroid Lipofuscinoses (Batten Disease) Panel
Neuronal Ceroid Lipofuscinosis 13 via the CTSF Gene
Neuronal Ceroid Lipofuscinosis 14 via the KCTD7 Gene
Neuronal Ceroid Lipofuscinosis 3 (Batten Disease) via the CLN3 c.461-280_677+382 Deletion

Citations

  • Benitez B.A. et al. 2011. Plos One. 6: e26741. PubMed ID: 22073189
  • Burneo J.G. et al. 2003. Epilepsia. 44: 841-6. PubMed ID: 12790899
  • Cadieux-Dion M. et al. 2013. Clinical Genetics. 83: 571-5. PubMed ID: 22978711
  • Dyken P.R. 1988. American journal of medical genetics. Supplement. 5: 69-84. PubMed ID: 3146331
  • Greaves J. et al. 2012. The Journal of Biological Chemistry. 287: 37330-9. PubMed ID: 22902780
  • 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. et al. 2011. American Journal of Human Genetics. 89: 241-52. PubMed ID: 21820099
  • Rider J.A., Rider D.L. 1988. American journal of medical genetics. Supplement. 5: 21-6. PubMed ID: 3146319
  • Schmitz F. et al. 2006. Proceedings of the National Academy of Sciences of the United States of America. 103: 2926-31. PubMed ID: 16477021
  • Schulz A. et al. 2004. Annals of neurology. 56: 342-50. PubMed ID: 15349861
  • Velinov M. et al. 2012. Plos One. 7: e29729. PubMed ID: 22235333
  • 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

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