Neuronal Ceroid Lipofuscinosis 10 via the CTSD 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
4131 CTSD 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4131CTSD81479 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

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). 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.

CLN10 has been associated with congenital onset, rapid progression and death during the first few weeks of life. Symptoms at onset include post-natal respiratory insufficiency, status epilepticus and microcephaly (Barohn et al. 1992). Previously, juvenile onset was considered to be an atypical form of CLN10 because only one case was reported in the literature (Steinfeld 2006). In this case, symptoms started during the early-school age, and included ataxia, retinitis pigmentosa and cerebral and cerebellar atrophy. Progressive cognitive and motor dysfunction developed later. Recently, two consanguineous families with a history of CLN10, similar features, and sensory axonal neuropathy were reported (Hersheson et al. 2014). In these two families symptoms started at age 8 and 15 years.

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). CLN10 is caused by compound heterozygous or homozygous pathogenic variants in the CTSD gene (Siintola et al. 2006; Steinfeld et al. 2006). Ten different pathogenic variants have been reported in various ethnic populations, including families from Somalia, Germany, the United States, and Pakistan. Eight of the variants are missense; the two remaining are expected to result in a truncated protein. No large pathogenic deletions have been reported to date (Human Gene Mutation Database).

Pathogenic variants in CTSD appear to be a rare cause of NCL. They account for about 1% of patients with a clinical diagnosis of the disorder (Santorell et al. 2013).

The CTSD gene encodes cathespsin D (CatD), a ubiquitously expressed lysosomal protease that is involved in several cellular functions, including proteolytic degradation (Baldwin et al. 1993). Complete or near complete deficiency of CatD activity causes a congenital and severe phenotype (Siintola et al. 2006; Fritchie et al. 2009); while a partial deficiency results in a juvenile phenotype (Steinfeld et al. 2006; Hersheson et al. 2014).

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in CTSD appear to be a rare cause of NCL. They account for about 1% of patients with a clinical diagnosis of the disorder (Santorelli et al. 2013).

Testing Strategy

This test provides full coverage of all coding exons of the CTSD 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 suggestive of neuronal ceroid lipofuscinosis. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CTSD.

Gene

Official Gene Symbol OMIM ID
CTSD 116840
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Ceroid Lipofuscinosis Neuronal 10 AR 610127

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

  • Baldwin ET. et al. 1993. Proceedings of the National Academy of Sciences of the United States of America. 90: 6796-800 PubMed ID: 8393577
  • Barohn RJ et al. 1992. Pediatric neurology. 8: 54–59. PubMed ID: 1558577
  • Dyken P.R. 1988. American journal of medical genetics. Supplement. 5: 69-84. PubMed ID: 3146331
  • Fritchie K. et al. 2009.  Acta neuropathologica. 117: 201–8. PubMed ID: 18762956
  • Hersheson J. et al. 2014. Neurology. 83: 1873-5. PubMed ID: 25298308
  • Human Gene Mutation Database (Bio-base).
  • 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
  • Rider J.A., Rider D.L. 1988. American journal of medical genetics. Supplement. 5: 21-6. PubMed ID: 3146319
  • Santorelli FM. et al. 2013. Orphanet journal of rare diseases. 8: 19. PubMed ID: 23374165
  • Schulz A. et al. 2004. Annals of neurology. 56: 342-50. PubMed ID: 15349861
  • Siintola E. et al. 2006. Brain : a journal of neurology. 129: 1438-45. PubMed ID: 16670177
  • Steinfeld R. et al. 2006. American journal of human genetics. 78: 988-98 PubMed ID: 16685649
  • Williams R.E., Mole S.E. 2012. Neurology. 79: 183-91. PubMed ID: 22778232

Ordering/Specimens

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  • 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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