Neuronal Ceroid Lipofuscinosis 7 via the MFSD8 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
3811 MFSD8 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3811MFSD881479 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 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.

CLN7 disease is characterized by late-infantile onset, usually between 2-7 years of age. It can be distinguished from the classical late-infantile CLN2 by more severe seizures and slower cerebral and cerebellar atrophy. Symptoms include ataxia, vision impairment and progressive cognitive and motor dysfunction (Kousi et al. 2009; Topcu et al. 2004).

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). CLN7 is caused by pathogenic variants in the MFSD8 gene (Siintola et al. 2007). To date, 35 different pathogenic variants have been reported in various ethnic populations. About half of the variants are missense. The other half is predicted to result in truncated proteins and include nonsense, splicing, small insertions or deletions, and indels. No large pathogenic deletions were reported to date (Human Gene Mutation Database). Pathogenic variants in MFSD8 account for about 40% of patients with late infantile neuronal ceroid lipofuscinosis. Most causative variants are unique to single families. A founder variant, c.881C>A (p.Thr294Lys), is common in the Roma population that originated from the former Czechoslovakia (Kousi et al. 2009; Kousi et al. 2012). The MFSD8 gene encodes the Major Facilitator Superfamily Domain-containing protein-8, a lysosomal membrane protein. It is hypothesized to be a lysosomal transporter. However, the nature of the transported substrates is unknown at this time (Siintola et al. 2007; Kousi et al. 2012).

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in MFSD8 were identified in about 40% of patients clinically diagnosed with late infantile ceroid lipofuscinoses (Kousi et al. 2009).

Testing Strategy

This test provides full coverage of all coding exons of the MFSD8 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, and late infantile onset. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in MFSD8.

Gene

Official Gene Symbol OMIM ID
MFSD8 611124
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Ceroid Lipofuscinosis Neuronal 7 AR 610951

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

  • Dyken P.R. 1988. American journal of medical genetics. Supplement. 5: 69-84. PubMed ID: 3146331
  • Human Gene Mutation Database (Bio-base).
  • Kousi M. et al. 2009. Brain : a journal of neurology. 132: 810-9. PubMed ID: 19201763
  • Kousi M. et al. 2012. Human mutation. 33: 42-63. PubMed ID: 21990111
  • 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
  • Schulz A. et al. 2004. Annals of neurology. 56: 342-50. PubMed ID: 15349861
  • Siintola E. et al. 2007. American journal of human genetics. 81: 136-46. PubMed ID: 17564970
  • Topçu M. et al. 2004. The Turkish journal of pediatrics. 46: 1-10. PubMed ID: 15074367
  • 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

Specimen Requirements and Shipping Details

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ORDER OPTIONS

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2) Select Additional Test Options

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

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