Bardet-Biedl Syndrome via the BBS4 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
6957 BBS4 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
6957BBS481479 81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

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

Turnaround Time

18 days on average

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Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder marked by primary features of obesity, polydactyly, pigmentary retinopathy, hypogonadism, renal anomalies, and mental retardation (Elbedour et al. Am J Med Genet 52(2):164-169, 1994; Sheffield. Trans Amer Clin Climatol Assoc 121:172-182, 2010). Secondary features include diabetes, hypertension, and congenital heart defects (Green et al. N Engl J Med 321(15):1002-1009, 1989). Although BBS is a rare condition, diagnosis is complicated by the fact that many of the clinical features (i.e. obesity, diabetes, hypertension, and developmental delay) are common. In addition, many of the BBS clinical features overlap with those of other well-described developmental disorders, including Meckel-Gruber syndrome (MKS; OMIM 249000), Joubert syndrome (JBTS; OMIM 213300), nephronophthisis (NPH; OMIM 256100), Senior-Loken syndrome (SLS; OMIM 609254), Leber congenital amaurosis (LCA; OMIM 204000), and Alstrom syndrome (OMIM 203800).

Genetics

BBS4 is primarily inherited as an autosomal recessive disorder, although complex inheritance has been reported in few families (Katsanis et al. Science 293:2256-2259, 2001). Variants in the BBS4 gene cause BBS (Mykytyn et al. Nat Genet 28:188-191, 2001). BBS4 encodes BBS4 protein, which is localized to basal bodies of the primary cilia (Kim et al. Nat Genet 36:462-470, 2004). BBS4 protein interacts with six other BBS proteins (BBS1, BBS2, BBS5, BBS7, BBS9, and BBS11) to form a complex known as BBSome, which has a role in cilia maintenance and function (Nachury et al. Cell 129:1201-1213, 2007). A mix of missense, splicing variants, and large deletions has been reported in BBS4 (Mykytyn et al. 2001; Katsanis et al. Am J Hum Genet 71:22-29, 2002). 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).

Testing Strategy

This test provides full coverage of all coding exons of the BBS4 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Clinical Sensitivity - Sequencing with CNV PG-Select

Variants in the BBS4 gene are estimated to cause approximately 3% of BBS cases (Katsanis et al. Am J Hum Genet 71:22-9, 2002).

Indications for Test

Candidates for this test are patients with symptoms consistent with BBS and the family members of patients who have known BBS4 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 BBS4.

Gene

Official Gene Symbol OMIM ID
BBS4 600374
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Bardet-Biedl Syndrome 4 AR 615982

Related Tests

Name
Bardet-Biedl Syndrome via the ARL6/BBS3 Gene
Bardet-Biedl Syndrome via the BBS2 Gene
Bardet-Biedl Syndrome via the BBS5 Gene
Bardet-Biedl Syndrome via the BBS9 Gene
Bardet-Biedl Syndrome via the MKKS/BBS6 Gene
Bardet-Biedl Syndrome via the TRIM32/BBS11 Gene
Joubert Syndrome, Meckel-Gruber Syndrome, and Nephronophthisis via the TMEM67 Gene
Nephronophthisis / Senior-Loken Syndrome and Bardet-Biedl Syndrome via the SDCCAG8 Gene

Citations

  • 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
  • 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
  • Katsanis, N., et.al. (2002). "BBS4 is a minor contributor to Bardet-Biedl syndrome and may also participate in triallelic inheritance." Am J Hum Genet 71(1): 22-9. PubMed ID: 12016587
  • Kim, J. C., et.al. (2004). "The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression." Nat Genet 36(5): 462-70. PubMed ID: 15107855
  • 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
  • Mykytyn, K., et.al. (2001). "Identification of the gene that, when mutated, causes the human obesity syndrome BBS4." Nat Genet 28(2): 188-91. PubMed ID: 11381270
  • Nachury MV, Loktev AV, Zhang Q, Westlake CJ, Peränen J, Merdes A, Slusarski DC, Scheller RH, Bazan JF, Sheffield VC, Jackson PK. 2007. A Core Complex of BBS Proteins Cooperates with the GTPase Rab8 to Promote Ciliary Membrane Biogenesis. Cell 129: 1201–1213. PubMed ID: 17574030
  • Sheffield, V.C. 2010. The blind leading the obese: the molecular pathophysiology of a human obesity syndrome. Trans Am Clin Climatol Assoc 121:172-182. PubMed ID: 20697559
  • Tobin, J. L., Beales, P. L. (2009). "The nonmotile ciliopathies." Genet Med 11(6): 386-402. PubMed ID: 19421068

Ordering/Specimens

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