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Mosaic Variegated Aneuploidy Syndrome via the BUB1B 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
BUB1B 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11115BUB1B81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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


  • Yuan Xue, PhD

Clinical Features and Genetics

Clinical Features

Mosaic Variegated Aneuploidy (MVA) syndrome is a rare disease generally characterized by prenatal growth retardation, microcephaly, mental retardation, central nervous system abnormalities, and cancer predisposition (García-Castillo et al., 2008; Callier et al., 2005). Cancers can include Wilms tumor, rhabdomyosarcoma and leukemia (Hanks et al., 2004). MVA syndrome can be caused by mutations in the BUB1B gene. Individuals with monoallelic BUB1B mutations are often severely affected with Dandy-Walker complex, cataracts and Wilms Tumor, and exhibit cellular premature chromatid separation (latter also known as Premature Chromatid Separation (PCS) Trait/ Syndrome); whereas individuals with biallelic BUB1B mutations have a moderate phenotype (García-Castillo et al., 2008). Interestingly, an individual with gastric neoplasia and without the characteristic features of MVA syndrome was found to have an intronic homozygous intronic BUB1B mutation (Rio Frio et al., 2010). Lastly, individuals who have MVA syndrome and who do not have a germline pathogenic variant in BUB1B or premature chromatid separation are mildly affected and rarely get cancer (García-Castillo et al., 2008).


MVA syndrome is generally considered a rare autosomal recessive disorder that can be caused by pathogenic variants in the BUB1B gene; however individuals can also be affected with only one pathogenic mutation present. At the cellular level, >10% of cells exhibit mosaic aneuploidies. In addition, approximately 2/3 of metaphases from patients show PCS (García-Castillo et al., 2008). The BUB1B gene's product (BUBR1) is thought to be involved in the mitotic spindle checkpoint, which includes several proteins that sense microtubule attachment to kinetochores. BUB1B mutations can cause defects in the mitotic spindle checkpoint, spindle attachment or cause reduction of BUBR1 protein levels (Suijkerbuijk et al., 2010). There does not appear to be preferential specific chromosome gains and losses, and thus trisomies and monosomies appear to be random (Hanks and Rahman, 2005). Interestingly, while BUB1B mutations can occur in individuals who are predisposed to cancer (MVA syndrome), BUB1B mutations are rarely observed in somatic cancers (Hanks et al., 2006). Most pathogenic variants are missense or nonsense, but other mutations such as splice site changes, small insertions and duplications have also been reported (Human Gene Mutation Database). Missense mutations tend to occur in or near the BUBR1 kinase domain (Suijkerbuijk et al. 2010), and biallelic mutations appear to usually consist of one truncating and one missense variant (Hanks et al. 2006).

Clinical Sensitivity - Sequencing with CNV PGxome

Analytical sensitivity should be high because the mutations reported are readily detectable by gene sequencing (Human Gene Mutation Database). Clinical sensitivity is unknown at this time since MVA syndrome is a rare disease and relatively few patients have been reported.

Testing Strategy

This test provides full coverage of all coding exons of the BUB1B 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

This test is useful for individuals who are suspected to have MVA syndrome, exhibit cellular PCS, have increased cytogenetic aneuploidies and/or familial carrier testing. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.


Official Gene Symbol OMIM ID
BUB1B 602860
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


  • Callier P, Faivre L, Cusin V, Marle N, Thauvin-Robinet C, Sandre D, Rousseau T, Sagot P, Lacombe E, Faber V, Mugneret F. 2005. Microcephaly is not mandatory for the diagnosis of mosaic variegated aneuploidy syndrome. American Journal of Medical Genetics Part A 137A: 204–207. PubMed ID: 16059936
  • García-Castillo H, Vásquez-Velásquez AI, Rivera H, Barros-Núñez P. 2008. Clinical and genetic heterogeneity in patients with mosaic variegated aneuploidy: delineation of clinical subtypes. Am. J. Med. Genet. A 146A: 1687–1695. PubMed ID: 18548531
  • Hanks S, Coleman K, Reid S, Plaja A, Firth H, Fitzpatrick D, Kidd A, Méhes K, Nash R, Robin N, Shannon N, Tolmie J, Swansbury J, Irrthum A, Douglas J, Rahman N. 2004. Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat. Genet. 36: 1159–1161. PubMed ID: 15475955
  • Hanks S, Coleman K, Summersgill B, Messahel B, Williamson D, Pritchard-Jones K, Strefford J, Swansbury J, Plaja A, Shipley J, Rahman N. 2006. Comparative genomic hybridization and BUB1B mutation analyses in childhood cancers associated with mosaic variegated aneuploidy syndrome. Cancer Lett. 239: 234–238. PubMed ID: 16182441
  • Hanks S, Rahman N. 2005. Aneuploidy-cancer predisposition syndromes: a new link between the mitotic spindle checkpoint and cancer. Cell Cycle 4: 225–227. PubMed ID: 15655355
  • Human Gene Mutation Database (Bio-base).
  • Suijkerbuijk SJE, van Osch MHJ, Bos FL, Hanks S, Rahman N, Kops GJPL. 2010. Molecular Causes for BUBR1 Dysfunction in the Human Cancer Predisposition Syndrome Mosaic Variegated Aneuploidy. Cancer Research 70: 4891–4900. PubMed ID: 20516114


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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View Ordering Instructions

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2) Select Additional Test Options

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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