Invitae Neuronal Ceroid Lipofuscinoses Panel

Ordering
  • Test code: 03405
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
Billing

Test description

The Invitae Neuronal Ceroid Lipofuscinoses Panel analyzes ten genes that are associated with neuronal ceroid lipofuscinosis (NCL), also known as Batten disease. This test is useful for the diagnosis of patients in whom NCL is suspected due to abnormal laboratory findings and clinical symptoms. Genetic testing of these genes may confirm a diagnosis and help guide management decisions.

Order test

Primary panel (10 genes)

CLN2 (TPP1) CLN3 CLN5 CLN6 CLN8 CTSD DNAJC5 KCTD7 MFSD8 PPT1

CLN3: Analysis includes the intronic variant NM_001042432.1; c.461-13G>C.
PPT1: Analysis includes the large, mostly intronic deletion NM_000310.3:c.124+1215_235-102del3627.

  • neuronal ceriod lipofuscinosis – also known as Batten disease
    • adult neuronal ceroid lipofuscinosis
    • congenital neuronal ceroid lipofuscinosis
    • CLN2 disease
    • infantile neuronal ceroid lipofuscinosis
    • juvenile neuronal ceroid lipofuscinosis
    • late-infantile neuronal ceroid lipofuscinosis
Gene Disorder
PPT1 CLN1
TPP1 CLN2
CLN3 CLN3
DNAJC5 CLN4
CLN5 CLN5
CLN6 CLN6
MFSD8 CLN7
CLN8 CLN8
CTSD CLN10
KCTD7 CLN14

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative lysosomal storage disorders that result in defective sphingolipid synthesis and the accumulation of autofluorescent ceroid lipopigments in the central nervous system. Symptom onset ranges from birth to adulthood. NCLs may be classified according to age of onset: congenital (before or around birth), infantile (6–24 months), late-infantile (2–8 years), juvenile (4–10 years), and adult (15+ years). Depending on the underlying gene, NCL can cause one or several clinical subtypes.

The NCLs are characterized by progressive decline, which can include psychomotor and cognitive decline, seizures, epilepsy, and early death. Most types of NCL, except for the adult form and Northern epilepsy, are associated with visual impairment that often progresses to blindness. In some NCLs, developmental delay, speech delay, ataxia, cerebellar and cerebral atrophy, hand stereotypies, sleep disturbances, behavioral/psychiatric disturbances, or additional brain MRI findings may develop. The age of onset and rate of disease progression are dependent on the underlying genetic condition.

Electron microscopy on lymphocytes or tissue biopsy may reveal characteristic histological findings among patients with NCL. CLN3 patients and some CLN8 patients will have vacuolated lymphocytes. Depending on the underlying genetic condition, NCL patients can also have granular osmiophilic deposits (GROD), predominantly curvilinear profiles (CVB), fingerprint profiles (FP), or a mixture of all three deposit types upon electron microscopy analysis of tissues; however, invasive procedures are needed to collect tissue specimens for such analysis. Patients with TPP1, PPT1, and CTSD will have low enzyme activity in leukocytes or fibroblasts of the respective enzyme. Due to the overlapping nature of these disorders and the lack of enzyme analyses available for all clinical subtypes, panel testing of NCLs using molecular approaches can reduce the time to diagnosis in many patients.

Although therapy is generally palliative or symptomatic, determining the underlying genetic cause can help guide management options: Some seizure medications and other types of medications may be contraindicated in these patients.

The clinical sensitivity of this test is dependent on the patient’s underlying genetic condition. This panel tests all of the known genetic causes of congenital, infantile, and late infantile NCL, as well as the majority of juvenile and adult NCL.

Gene Disorder Estimated clinical sensitivity
PPT1 CLN1 >98%
TPP1 CLN2 >97%
CLN3 CLN3 >98%
DNAJC5 CLN4 >95%
CLN5 CLN5 >90%–95%
CLN6 CLN6 >92%
MFSD8 CLN7 >95%
CLN8 CLN8 >90%–95%
CTSD CLN10 >95%
KCTD7 CLN14 >95%

All forms of NCL tested in this panel are inherited in an autosomal recessive manner.

The NCLs have an estimated prevalence of 1 in 112,000–670,000.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
CLN2 (TPP1) NM_000391.3
CLN3* NM_001042432.1
CLN5 NM_006493.2
CLN6 NM_017882.2
CLN8 NM_018941.3
CTSD NM_001909.4
DNAJC5 NM_025219.2
KCTD7 NM_153033.4
MFSD8 NM_152778.2
PPT1* NM_000310.3

CLN3: Analysis includes the intronic variant NM_001042432.1; c.461-13G>C.
PPT1: Analysis includes the large, mostly intronic deletion NM_000310.3:c.124+1215_235-102del3627.