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Hereditary Diffuse Leukoencephalopathy with Spheroids via the CSF1R Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
CSF1R 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
10665CSF1R81479 81479,81479 $990 Order Options and Pricing

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

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


  • Li Fan, MD, PhD, FCCMG, FACMG

Clinical Features and Genetics

Clinical Features

CSF1R-related disorders comprise two conditions and phenotypes. One is hereditary diffuse leukoencephalopathy with spheroids, which is a rapidly progressive neurodegenerative disorder with adult-onset. The mean age of onset is 43 years (18–78 years), and women have a significantly younger age of onset than men. The major symptoms include cognitive impairment, memory loss, dementia, Parkinsonism, apraxia, rigidity, bradykinesia, shuffling gait, spasticity, and seizures. The minor features include depression and behavioral changes. Brain MRI shows diffusion-restricted lesions and calcifications in the white matter, thin corpus callosum and abnormal signal in pyramidal tracts, dilation of the lateral ventricles and cortical atrophy. The phenotype of this disease is also affected by sex. For example, in addition to a significantly younger age of onset than men, motor dysfunctions were the most frequent initial symptom in women (Karle et al. 2013. PubMed ID: 24198292; Konno et al. 2014. PubMed ID: 24336230; Konno et al. 2017. PubMed ID: 27680516; Abe et al. 2017. PubMed ID: 28025469).

The other condition is brain abnormalities with neurodegeneration and dysosteosclerosis. Onset can be as early as prenatal (Oosterhof et al. 2019. PubMed ID: 30982608). The major symptoms include structural brain anomalies, skeletal dysplasia, dysosteosclerosis, and osteopetrosis. Some patients may have dysmorphic facial features (Oosterhof et al. 2019. PubMed ID: 30982608; Guo et al. 2019. PubMed ID: 30982609).

As leukoencephalopathy can be caused by defects in hundreds of genes with variable and overlapping presentations, it is difficult to diagnose by clinical manifestation and image studies. An accurate molecular diagnosis is critical for treatment, prognosis, and prediction of recurrence risk as well as future family planning.


Hereditary diffuse leukoencephalopathy with spheroids is inherited in an autosomal dominant manner whereas CSF1R-related brain abnormalities with neurodegeneration and dysosteosclerosis is inherited in an autosomal recessive manner. Pathogenic variants in CSF1R include missense, nonsense, splicing, and small deletions and duplications. Large deletions and complex rearrangements have also been reported in the CSF1R locus (Human Gene Mutation Database). De novo pathogenic variants were found in one-third of patients (Karle et al. 2013. PubMed ID: 24198292). Seventy-nine percent of the pathogenic variants were located in the distal part of the tyrosine kinase domain of CSF1R (Konno et al. 2017. PubMed ID: 27680516).

CSF1R encodes a tyrosine kinase growth factor receptor for colony-stimulating factor 1, the macrophage- and monocyte-specific growth factor. CSF1R is expressed in microglia, which is important for neuronal and brain development, and in osteoclasts, which plays an essential role in bone mineralization. A zebrafish model (csf1rDM) with Csf1r malfunction showed brains that lacked microglia (Oosterhof et al. 2019. PubMed ID: 30982608). This is also supported by a knock-out mouse model of Csf1r-null presenting various anatomical abnormalities in developing brains, and sclerosing skeletal dysplasia, which eventually resulted in death (Guo et al. 2019. PubMed ID: 30982609; Erblich et al. 2011. PubMed ID: 22046273; Dai et al. 2002. PubMed ID: 11756160).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity of CSF1R testing is high. Pathogenic variants in CSF1R were detected in 6 of 7 patients with hereditary diffuse leukoencephalopathy with spheroids (Konno et al. 2014. PubMed ID: 24336230).

Testing Strategy

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

This test provides full coverage of all coding exons of the CSF1R gene 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 full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

CSF1R sequencing is recommended for patients who are suspected to have hereditary diffuse leukoencephalopathy with spheroids as well as CSF1R-related brain abnormalities with neurodegeneration and dysosteosclerosisTargeted testing is indicated for family members of patients who have a known pathogenic variant in CSF1R. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CSF1R.


Official Gene Symbol OMIM ID
CSF1R 164770
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


  • Abe et al. 2017. PubMed ID: 28025469
  • Dai et al. 2002. PubMed ID: 11756160
  • Erblich et al. 2011. PubMed ID: 22046273
  • Guo et al. 2019. PubMed ID: 30982609
  • Human Gene Mutation Database (Bio-base).
  • Karle et al. 2013. PubMed ID: 24198292
  • Konno et al. 2014. PubMed ID: 24336230
  • Konno et al. 2017. PubMed ID: 27680516
  • Oosterhof et al. 2019. PubMed ID: 30982608


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

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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