Niemann-Pick Disease Type C Panel

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
3425 NPC1 81406,81479 Order Options and Pricing
NPC2 81404,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
3425Genes x (2)81479 81404, 81406, 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

Niemann-Pick disease Type C (NPC) is a lipid storage disorder in which defects in the intracellular transport and trafficking of low-density lipoprotein (LDL)-derived cholesterol result in the accumulation of cholesterol and other lipids in tissues. NPC has a prevalence of 1:90,000 to 100,000 live births although this may be an underestimate due to the clinical heterogeniety of the disorder (Papandreou and Gissen 2016). The disease is characterized by extensive clinical heterogeneity with respect to the age of onset, initial symptoms, severity, and progression. NPC can present at any time from intrauterine to the sixth decade with liver failure, incidental organomegaly, or a wide variety of neurological and psychiatric symptoms. Most common clinical features include enlarged spleen and liver, jaundice, dystonia, seizures, tremor, ataxia, vertical supranuclear gaze palsy, learning difficulty and slurred speech (Patterson 2003; Vanier and Millat 2003; Papandreou and Gissen 2016). Cases with fetal onset, detected ultrasonically in the form of severe ascites, have been reported (Maconochie 1989; Manning et al. 1990; Spiegel et al. 2009). NPC occurs worldwide; it is however more common in two genetic isolates: a French isolate originating from Normandy and settling in Nova Scotia (Millat et al. 1999); and an Hispanic isolate originating from the Upper Rio Grande Valley in the USA and settling in New Mexico and Colorado (Wenger et al. 1977).

Genetics

NPC is inherited in an autosomal recessive manner and is further divided into two subtypes, NPC1 and NPC2, based on the causative gene. Clinically, NPC1 and NPC2 are identical. NPC1 accounts for ~95% of cases and is caused by variants in the NPC1 gene (Carstea et al. 1997; Papandreau and Gissen 2016). The NPC1 gene encodes a lysosomal-endosomal transmembrane protein required for the egress of lipids from the lysosome. Over 400 pathogenic variants, distributed throughout the gene, have been reported and include missense/nonsense (~70%), small insertion/deletions (~22%) and splicing (< 1%). Gross insertions and deletions are apparently rare (Human Gene Mutation Database). Two founder mutations have been identified. The p.Gly992Trp variant was found in all patients from the Nova Scotia isolate (Greer et al. 1998). The p.Ile1061Thr variant, which apparently originated in Western Europe, was detected in all Hispanic patients from the Upper Rio Grande isolate (Millat et al. 1999).

NPC2 accounts for ~4% of cases and is caused by variants in the NPC2 gene (Papandreau and Gissen 2016). The NPC2 gene encodes a soluble lysosomal protein with cholesterol binding properties; it is required for the egress of lipids from the lysosomes. To date, 25 pathogenic variants have been reported in NPC2 including missense/nonsense (~76%), splicing (~12%), and small deletions (~12%). No large deletions or duplications have been reported in NPC2 (Human Gene Mutation Database).

The remaining ~1% of cases of NPC are biochemically-confirmed cases with no identified variants in NPC1 or NPC2.

Clinical Sensitivity - Sequencing with CNV PG-Select

This test is be expected to detect variants in >95% of individuals with biochemically-confirmed NPC (Papandreou and Gissen 2016).

Although rare, gross deletions and duplications have been reported in the NPC1 gene. None of the variants reported to date in NPC2 have been gross deletions or duplications (Human Gene Mutation Database).

Testing Strategy

This panel provides 100% coverage of all coding exons of the genes listed, plus ~10 bases of flanking noncoding DNA. We define coverage as ≥20X NGS reads or Sanger sequencing.

Indications for Test

This test is appropriate for all patients with clinical features suggestive of NPC and asymptomatic carrier relatives. Candidates for this test may also include: (1) Patients with unexplained dementia or psychiatric illness and cognitive impairment, particularly when accompanied by ataxia, dystonia, or vertical supranuclear gaze palsy, (2) infants with unexplained cholestatic jaundice, and (3) older children with progressive liver disease (Patterson 2003).

Genes

Official Gene Symbol OMIM ID
NPC1 607623
NPC2 601015
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Carstea E.D. et al. 1997. Science. 277: 228-31. PubMed ID: 9211849
  • Greer W.L et al. 1998. American Journal of Human Genetics. 63: 52-4. PubMed ID: 9634529
  • Human Gene Mutation Database (Bio-base).
  • Maconochie I.K. et al. 1989. Archives of Disease in Childhood. 64: 1391-3. PubMed ID: 2589877
  • Manning D.J. et al. 1990. Archives of Disease in Childhood. 65: 335-6. PubMed ID: 2334227
  • Millat G. et al. 1999. American Journal of Human Genetics. 65: 1321-9. PubMed ID: 10521297
  • Papandreou A., Gissen P. 2016. Therapeutic Advances in Neurological Disorders. 9: 216-29. PubMed ID: 27134677
  • Patterson M.C. 2003. The Neurologist. 9: 301-10. PubMed ID: 14629784
  • Spiegel R. et al. 2009. American Journal of Medical Genetics. Part A. 149A: 446-50. PubMed ID: 19206179
  • Vanier M.T., Millat G. 2003. Clinical Genetics. 64: 269-81. PubMed ID: 12974729
  • Wenger D.A. et al. 1977. American Journal of Diseases of Children. 131: 955-61. PubMed ID: 900082

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

Specimen Requirements and Shipping Details

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Total Price: $
×
Copy Text to Clipboard
×