Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10103 TREM2 81479,81479 Order Options and Pricing
TYROBP 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10103Genes x (2)81479 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

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

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), also known as Nasu-Hakola disease, is a progressive neurodegenerative disease characterized by multiple bone cysts and early frontal lobe dementia. Pain in the hands and feet, followed by recurrent fractures of the wrists and ankles are usually the first symptoms. They appear during the third decade of life. Frontal lobe symptoms appear later and include behavioral changes, memory loss, euphoria, inappropriate social conduct, disinhibition, and loss of verbal fluency. They are usually accompanied by upper motor neuron symptoms in the form of spasticity, generalized seizures and gait disturbance. Neuroimaging and neuropathological findings indicate cerebral and cerebellar atrophy, demyelination of the cerebral white matter, and calcification of the basal ganglia (Ohtani et al. 2014). The disease progresses relatively rapidly, and death occurs by the end of the fifth decade of life (Bird et al. 1983; Verloes et al. 1977; Paloneva et al. 2001).

PLOSL is clinically heterogeneous. Fractures and bone cysts have been identified in the majority of the reported cases. However, patients with no apparent bone involvement have been documented, prompting a recommendation for ankles and wrists radiography in patients with frontal lobe dementia of unknown etiology (Paloneva et al. 2001; Chouery et al. 2008; Yamazaki et al. 2015).

PLOSL is rare with less than 1/1,000,000 people affected. Although most cases have been reported in the Japanese, Finnish and Swedish populations, patients have been reported worldwide (Pekkarinen et al. 1998; Klunemann et al. 2005).

Genetics

PLOSL is inherited in an autosomal recessive manner. It is caused by defects in one of two genes: TYROBP or TREM2. Pathogenic variants in TYROBP account for 79% of patients with a clinical diagnosis and MRI findings of PLOSL; and pathological variants in TREM2 account for about 21% of patients (Paloneva et al. 2002). They have been reported in patients from various ethnic and geographical populations.

To date, about 10 different pathogenic variants have been reported in TYROBP and TREM2 each. The majority is predicted to result in truncated proteins and includes nonsense, splicing, and small deletions or insertions (Paloneva et al. 2000; Kondo et al. 2002; Paloneva et al. 2002; Klünemann et al. 2005). Large pathogenic deletions appear to be rare. Only one such deletion has been reported in TYROBP (Paloneva et al. 2000); while none have been reported in TREM2 (Human Gene Mutation Database).

The TREM2 gene encodes Triggering Receptor Expressed on Myeloid cells 2. The TYROBP gene encodes Tyrosine Kinase Binding Adaptor Protein. The encoded proteins form two different subunits of a receptor-signaling complex. The TREM2-TYROBP complex is involved in the regulation of immune responses, the phagocytic activity of microglia, and the differentiation of dendritic cells and osteoclasts (Turnbull et al. 2006). In vitro studies revealed that pathogenic variants in either gene result in a reduction of bone resorption capacity in osteoclasts (Cella et al. 2003; Humphrey et al. 2006).

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in the TREM2-TYROBP complex appear to account for the vast majority of patients with clinical and MRI findings suggestive of PLOSL. TYROBP variants were identified in 79% of patients, and TREM2 variants in 21% of patients. All patients presented with identical features (Paloneva et al. 2002).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

All patients with symptoms and MRI findings suggestive of PLOSL with or without bone involvement (Paloneva et al. 2000; Paloneva et al. 2002; Chouery et al. 2008).

Genes

Official Gene Symbol OMIM ID
TREM2 605086
TYROBP 604142
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Bird T.D. et al. 1983. Neurology. 33: 81-6. PubMed ID: 6681564
  • Cella M. et al. 2003. The Journal of Experimental Medicine. 198: 645-51. PubMed ID: 12913093
  • Chouery E. et al. 2008. Human Mutation. 29: E194-204. PubMed ID: 18546367
  • Human Gene Mutation Database (Bio-base).
  • Humphrey M.B. et al. 2006. Journal of Bone and Mineral Research. 21: 237-45. PubMed ID: 16418779
  • Klünemann H.H. et al. 2005. Neurology. 64: 1502-7. PubMed ID: 15883308
  • Kondo T. et al. 2002. Neurology. 59: 1105-7. PubMed ID: 12370476
  • Ohtani R. et al. 2014. Internal Medicine. 53: 2407. PubMed ID: 25318814
  • Paloneva J. et al. 2001. Neurology. 56: 1552-8. PubMed ID: 11402114
  • Paloneva J. et al. 2000. Nature Genetics. 25: 357-61. PubMed ID: 10888890
  • Paloneva J. et al. 2002. American Journal of Human Genetics. 71: 656-62. PubMed ID: 12080485
  • Pekkarinen P. et al. 1998. American Journal of Human Genetics. 62: 362-72. PubMed ID: 9463329
  • Turnbull I.R. et al. 2006. Journal of Immunology. 177: 3520-4. PubMed ID: 16951310
  • Verloes A. et al. 1997. Journal of Medical Genetics. 34: 753-7. PubMed ID: 9321763
  • Yamazaki K. et al. 2015. Clinical Psychopharmacology and Neuroscience. 13: 324-6. PubMed ID: 26598595

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

View Ordering Instructions

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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.

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