Cherubism via the SH3BP2 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
1288 SH3BP2$840.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity
Mutations in the SH3BP2 gene can be identified in at least 80% of individuals affected with Cherubism (Baskin et al. 2001).

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Clinical Features
Cherubism results in painless bilateral growths in the mandible and/or maxilla (Baskin et al. 2001). The fibrous cyst-like growths result in a swollen round facial appearance, which can interfere with normal tooth development causing premature loss of the primary teeth and uneruption of the permanent teeth. There is quite a range of phenotype appearance with affected individuals with mild features, and others where the growths interfere with vision, breathing, speech, and swallowing (Pérez-Sayáns et al. 2013). The growths usually begin between 2-7 years of age and progress through childhood and stabilize at puberty and then partial or total regression occurs (Kömerik et al. 2013). Cherubism does not affect intelligence and an affected individual is otherwise physically normal. At least 250 cases have been reported worldwide (Preda et al. 2010).
Cherubism is a rare autosomal dominant disorder which shows variable expressivity with near complete penetrance in males and reduced penetrance in females (Baskin et al. 2001; Pérez-Sayáns et al. 2013). It is caused by pathogenic variants in the SH3BP2 gene, which encodes a protein that binds to SH3 domains of several proteins, such as protein tyrosine kinases, involved in maintenance of bone tissue and specific immune cells (Lietman et al. 2008). Most reported pathogenic variants cluster in one area of the gene, but other mutations have been reported outside of this region (Carvalho et al. 2009). Reported causative mutations are mostly missense variants, but a small deletion has also been reported that caused an aggressive form of Cherubism (Carvalho et al. 2008).
Testing Strategy
The SH3 domain-binding protein 2 is encoded by 12 exons (5-16) from the SH3BP2 gene on chromosome 4p16.3. Testing is accomplished by amplifying each coding exon and ~20 bp of adjacent noncoding sequence, then determining the nucleotide sequence using standard Sanger dideoxy sequencing methods and a capillary electrophoresis instrument. We will also sequence any single exon (Test #100) in family members of patients with a known mutation or to confirm research results.
Indications for Test
Individuals with a clinical presentation of Cherubism and individuals with a family history.


Official Gene Symbol OMIM ID
SH3BP2 602104
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Cherubism 118400


Genetic Counselors
  • Baskin B, Bowdin S, Ray PN. 2001. Cherubism. 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: 20301316
  • Carvalho V, Perdigão P, Amaral F, Souza P de, Marco L De, Gomez R. 2009. Novel mutations in the SH3BP2 gene associated with sporadic central giant cell lesions and cherubism. Oral Diseases 15: 106–110. PubMed ID: 19017279
  • Carvalho VM, Perdigão PF, Pimenta FJ, Souza PEA de, Gomez RS, Marco L De. 2008. A novel mutation of the SH3BP2 gene in an aggressive case of cherubism. Oral Oncology 44: 153–155. PubMed ID: 17368082
  • Kömerik N, Taş B, Önal L. 2013. Cherubism. Head and Neck Pathology. PubMed ID: 24037598
  • Lietman SA, Yin L, Levine MA. 2008. SH3BP2 is an activator of NFAT activity and osteoclastogenesis. Biochemical and Biophysical Research Communications 371: 644–648. PubMed ID: 18440306
  • Pérez-Sayáns M, Barros-Angueira F, Suárez-Peñaranda JM, García-García A. 2013. Variable expressivity familial cherubism: woman transmitting cherubism without suffering the. PubMed ID: 24382142
  • Preda L, Dinca O, Bucur A, Dragomir C, Severin E. 2010. Identical Mutation in SH3BP2 Gene Causes Clinical Phenotypes with Different Severity in Mother and Daughter – Case Report. Molecular Syndromology 1: 87–90. PubMed ID: 21045962
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 20 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of March 2016, we compared 17.37 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 12 years of our lab operation we have Sanger sequenced roughly 8,800 PCR amplicons. Only one error has been identified, and this was due to sequence analysis error.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 20 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

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Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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