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TREM2-Related Disorders via the TREM2 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
TREM2 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8931TREM281479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

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

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

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


Genetic Counselors


  • Sali Farhan, PhD

Clinical Features and Genetics

Clinical Features

1- 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. 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 worldwide. Although most cases have been reported in the Japanese, Finnish and Swedish populations, patients have been reported worldwide (Pekkarinen et al. 1998).

2- Frontotemporal dementia (FTD), previously referred to as Pick’s disease, is a clinically heterogeneous syndrome due to the progressive degeneration and atrophy of various regions of the frontal and temporal lobes of the brain. MRI findings reveal frontal and/or temporal atrophy. Symptoms are insidious and begin usually during the fourth to sixth decades of life; although earlier and later onset have been documented (Snowden et al. 2002; Bruni et al. 2007 ).

Two major forms, behavioral-variant (FTD-bv) and primary progressive aphasia (PPA), are recognized based on the site of onset of degeneration and the associated symptoms.

In FTD-bv the degenerative process begins in the frontal lobes and results in personality changes and deterioration of social conducts. Most common behavioral changes are: disinhibition, apathy, deterioration of executive function, obsessive thoughts, compulsive behavior, and neglect of personal hygiene.

In PPA the degenerative process begins in the temporal lobes. PPA is a language disorder that is further divided into two sub-forms: progressive non-fluent aphasia (PNFA) and semantic dementia (SD). PNFA is characterized by difficulty in verbal communications, word retrieval, and speech distortion. Reading, writing and spelling are also affected; while memory is relatively preserved. SD is characterized by the progressive impairment of word comprehension, object and face recognition, and loss of semantic memory. Reading and writing skills are relatively preserved (Gustafson et al. 1993).

The clinical diagnosis of FTD is based on the combination of medical history, physical and neurological examination, brain imaging, and neuropsychological and psychiatric assessment (Neary et al. 1998; Snowden 2002; Rascovsky et al 2011; Mesulam 2001).

FTD affects people worldwide, with a prevalence of up to 15 per 100,000 (Ratnavalli et al. 2002). It is the second most common dementia in people under the age of 65 years, after Alzheimer's disease, accounting for up to 20% of presenile dementia cases (Snowden et al. 2002).

3. Frontotemporal dementia-like syndrome, also known as FTD-like disease, is an atypical form of frontotemporal dementia. Its distinguishing clinical features include epileptic seizures, parkinsonism, abnormal eye movements, and hallucinations. Atypical MRI findings indicate white matter abnormalities and thinning of the corpus callosum. There is no bone involvement in FTD-like disease. Symptoms appear during the third decade of life and death occurs during the fourth decade (Guerreiro et al. 2013a; Guerreiro et al. 2013b; Le Ber et al. 2014).


1- PLOSL is inherited in an autosomal recessive manner. It is caused by pathogenic variants in either the TREM2 or TYROBP genes (Paloneva et al. 2000; Paloneva et al. 2002). To date, 11 different pathogenic variants in TREM2 have been reported in patients with PLOSL from various ethnic and geographical populations (Paloneva et al. 2002; Klünemann et al. 2005). The majority is predicted to result in truncated proteins and includes nonsense, splicing, and small deletions. Only three missense variants have been reported. No large pathogenic deletions in TREM2 have been reported to date (Human Gene Mutation Database).

2- FTD is inherited in about 40% of cases (Rosso et al. 2003). In these families, the disease is inherited in an autosomal dominant manner. The remaining cases appear to be simplex with no known affected relatives. It is, however, unclear how many of the apparently sporadic cases are inherited with low penetrance (Cruts et al. 2006; Le Ber et al. 2007).

FTD is genetically heterogeneous. Several genes have been implicated in the disorder: C9orf72, GRN, MAPT, CHMPEB, TARDBP, FUS and VCP.

At this time no pathogenic variants in TREM2 were reported to be a primary cause of FTD. However, results obtained from association studies suggested that heterozygous TREM2 variants are associated with an increased predisposition to FTD and other neurodegenerative disorders (Giraldo et al. 2013a; Guerreiro et al. 2013c).

3- FTD-like disease is inherited with an autosomal recessive manner, another distinguishing feature from FTD. Homozygous and compound heterozygous pathogenic variants in TREM2 have been identified in patients with autosomal recessive FTD-like disease and no bone involvement. Six variants were initially identified by whole genome or whole exome sequencing in six families from Libanon, Turkey, Columbia and Italy. These include one splice site, two nonsense and three missense (Chouery et al. 2008; Giraldo et al. 2013; Guerreiro et al. 2013a; 2013b; Le Ber et al. 2014).

The TREM2 gene encodes Triggering Receptor Expressed on Myeloid cells 2, and forms a receptor signaling complex with a tyrosine kinase binding adaptor protein TYROBP. The TREM2- TYROBP complex is involved in the regulation of immune responses, the differentiation of dendritic cells and osteoclasts, and in the phagocytic activity of microglia (Turnbull et al. 2006; Xing et al. 2015).

Clinical Sensitivity - Sequencing with CNV PG-Select

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

TREM2 pathogenic variants were reported in about 6% of patients with frontotemporal-dementia-like syndrome (Guerreiro et al. 2013a).

Testing Strategy

This test provides full coverage of all coding exons of the TREM2 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

All patients with symptoms and MRI findings suggestive of PLOSL or FTD-like disease with or without bone involvement (Paloneva et al. 2000; Paloneva et al. 2002; Chouery et al. 2008). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in TREM2.


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

Related Test

Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy Panel


  • Bird T.D. et al. 1983. Neurology. 33: 81-6. PubMed ID: 6681564
  • Bruni A.C. et al. 2007. Neurology. 69: 140-7. PubMed ID: 17620546
  • Chouery E. et al. 2008. Human Mutation. 29: E194-204. PubMed ID: 18546367
  • Giraldo M. et al. 2013. Neurobiology of Aging. 34: 2077.e11-8. PubMed ID: 23582655
  • Guerreiro R. et al. 2013b. Neurobiology of Aging. 34: 2890.e1-5. PubMed ID: 23870839
  • Guerreiro R. et al. 2013c. The New England Journal of Medicine. 368: 117-27. PubMed ID: 23150934
  • Guerreiro R.J. et al. 2013a. Jama Neurology. 70: 78-84. PubMed ID: 23318515
  • Gustafson L. 1993. Dementia. 4: 143-8. PubMed ID: 8401782
  • Human Gene Mutation Database (Bio-base).
  • Klünemann H.H. et al. 2005. Neurology. 64: 1502-7. PubMed ID: 15883308
  • Le Ber I. et al. 2014. Neurobiology of Aging. 35: 2419.e23-5. PubMed ID: 24910390
  • Mesulam M.M. 2001. Primary progressive aphasia. Ann. Neurol. 49: 425–432. PubMed ID: 11310619
  • Neary D. et al. 1998. Neurology. 51: 1546-54. PubMed ID: 9855500
  • 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
  • Paloneva  J. et al. 2001. Neurology. 56: 1552-8. PubMed ID: 11402114
  • Pekkarinen P. et al. 1998. American Journal of Human Genetics. 62: 362-72. PubMed ID: 9463329
  • Rascovsky K. et al. 2011. Brain : a Journal of Neurology. 134: 2456-77. PubMed ID: 21810890
  • Ratnavalli E. et al. 2002. Neurology. 58: 1615-21. PubMed ID: 12058088
  • Rosso S.M. et al. 2003. Brain : a Journal of Neurology. 126: 2016-22. PubMed ID: 12876142
  • Snowden J.S. 2002. Frontotemporal dementia. The British Journal of Psychiatry 180: 140-3. PubMed ID: 11823324
  • Turnbull I.R. et al. 2006. Journal of Immunology (baltimore, Md. : 1950). 177: 3520-4. PubMed ID: 16951310
  • Verloes A. et al. 1997. Journal of Medical Genetics. 34: 753-7. PubMed ID: 9321763
  • Xing J. et al. 2015. Research and Reports in Biochemistry. 5: 89-100. PubMed ID: 26478868
  • Yamazaki K. et al. 2015. Clinical Psychopharmacology and Neuroscience : the Official Scientific Journal of the Korean College of Neuropsychopharmacology. 13: 324-6. PubMed ID: 26598595


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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

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