Bardet-Biedl Syndrome via the TRIM32/BBS11 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 15209 | TRIM32 | 81479 | 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.
Clinical Features and Genetics
Clinical Features
Bardet-Biedl syndrome (BBS) is characterized by retinal degeneration, obesity, post-axial polydactyly, cognitive impairment, hypogenitalism, and renal and cardiovascular anomalies (Green et al. N Engl J Med 321:1002-1009, 1989; Elbedour et al. Am J Med Genet 52:164-169, 1994). Limb-girdle muscular dystrophy type 2H (LGMD2H) (OMIM# 254110) is a mild myopathy characterized by muscle weakness and wasting restricted to the proximal limbs (Frosk et al. Hum Mutat 25:38-44, 2005). Both LGMD2H and Bardet-Biedl syndrome 11 (BBS11) (OMIM# 602290) are caused by variants in TRIM32/BBS11 gene (Forsk et al. 2005; Chiang et al. Proc Nat Acad Sci USA103:6287-6292, 2006).
Genetics
LGMD2H and BBS are inherited as autosomal recessive disorders, although complex inheritance has been reported in a few BBS families (Katsanis et al. Science 293:2256-2259, 2001). TRIM32/BBS11 encodes a tripartite motif (TRIM)-containing protein 32 (TRIM32). TRIM32 has domain structure composed of a RING finger, a B-box, and a coiled-coil motif important for E3 ubiquitin ligase activity, along with five C-terminal NHL repeats important for protein-protein interaction (Kudryashova et al. J Molec Biol 354:413-424, 2005). Although the precise function of TRIM32 is not yet known, TRIM32 has been implicating in regulating components of the cytoskeleton (Kudryashova et al. 2005). A TRIM32 missense variant (p.Pro130Leu) has been reported in a BBS family (Chiang et al. Proc Nat Acad Sci USA 103:6287-6292, 2006). BBS exhibits locus heterogeneity; at least 12 BBS genes have been identified (BBS1, BBS2, BBS3, BBS4, BBS5, MKKS/BBS6, BBS7, TTC8/BBS8, BBS9, BBS10, TRIM32/BBS11, and BBS12) (Tobin and Beales, Genet Med 11:386-402, 2009). In addition, hypomorphic variants in two Meckel-Gruber syndrome genes (MKS1 and CEP290) were reported to be associated with BBS, representing BBS13 and BBS14 respectively (Leitch et al. Nat Genet 40:443-448, 2008).
Clinical Sensitivity - Sequencing with CNV PG-Select
Variants in the TRIM32/BBS11 gene are estimated to cause < 1% of BBS cases (Chiang et al. Proc Natl Acad Sci USA 103:6287-6292, 2006).
Testing Strategy
This test is performed using Next-Generation sequencing with additional Sanger sequencing as necessary.
This test provides full coverage of all coding exons of the TRIM32 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Candidates for this test are patients with symptoms consistent with BBS and the family members of patients who have known TRIM32/BBS11 variants. Conclusive connections between clinical features and individual mutated BBS genes have not yet been made. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in TRIM32.
Candidates for this test are patients with symptoms consistent with BBS and the family members of patients who have known TRIM32/BBS11 variants. Conclusive connections between clinical features and individual mutated BBS genes have not yet been made. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in TRIM32.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| TRIM32 | 602290 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Bardet-Biedl Syndrome 11 | AR | 615988 |
Citations
- Chiang, A. P., et.al. (2006). "Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11)." Proc Natl Acad Sci USA 103(16): 6287-92. PubMed ID: 16606853
- Elbedour K, Zucker N, Zalzstein E, Barki Y, Carmi R. 1994. Cardiac abnormalities in the Bardet-Biedl syndrome: echocardiographic studies of 22 patients. Am. J. Med. Genet. 52: 164–169. PubMed ID: 7802002
- Frosk, P., et.al. (2005). "The most common mutation in FKRP causing limb girdle muscular dystrophy type 2I (LGMD2I) may have occurred only once and is present in Hutterites and other populations." Hum Mutat 25(1): 38-44. PubMed ID: 15580560
- Green JS, Parfrey PS, Harnett JD, Farid NR, Cramer BC, Johnson G, Heath O, McManamon PJ, O’Leary E, Pryse-Phillips W. 1989. The cardinal manifestations of Bardet–Biedl syndrome, a form of Laurence–Moon–Biedl syndrome. New England Journal of Medicine 321: 1002–1009. PubMed ID: 2779627
- Katsanis N, Ansley SJ, Badano JL, Eichers ER, Lewis RA, Hoskins BE, Scambler PJ, Davidson WS, Beales PL, Lupski JR. 2001. Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder. Science 293: 2256–2259. PubMed ID: 11567139
- Kudryashova, E., et.al. (2005). "Trim32 is a ubiquitin ligase mutated in limb girdle muscular dystrophy type 2H that binds to skeletal muscle myosin and ubiquitinates actin." J Mol Biol 354(2): 413-24. PubMed ID: 16243356
- Leitch CC, Zaghloul NA, Davis EE, Stoetzel C, Diaz-Font A, Rix S, Al-Fadhel M, Lewis RA, Eyaid W, Banin E, Dollfus H, Beales PL, et al. 2008. Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome. Nature Genetics 40: 443–448. PubMed ID: 18327255
- Tobin, J. L., Beales, P. L. (2009). "The nonmotile ciliopathies." Genet Med 11(6): 386-402. PubMed ID: 19421068
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.
- 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
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