Journal of Cell Biology and Genetics
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Article Number - 3834F5B822


Vol.1(1), pp. 1 - 11 , September 2010

ISSN: 2141-6516



Review

Molecular variants of Bardet-Biedl Syndrome



Hina Iqbal
  • Hina Iqbal
  • Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
  • Google Scholar
Hussain Mustatab Wahedi
  • Hussain Mustatab Wahedi
  • Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
  • Google Scholar
Fauzia Yusuf Hafeez
  • Fauzia Yusuf Hafeez
  • Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
  • Google Scholar
Asif Mir
  • Asif Mir
  • Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
  • Google Scholar







 Accepted: 04 February 2010  Published: 30 September 2010

Copyright © 2010 Author(s) retain the copyright of this article.
This article is published under the terms of the Creative Commons Attribution License 4.0


Bardet-Biedl Syndrome (BBS) is a genetically and clinically heterogeneous disorder clinically characterized by obesity, mental retardation, dysphormic extremities (syndactyly, brachydactyly or polydactyly), retinal dystrophy or pigmentary retinopathy, hypogonadism and kidney structural abnormalities or functional impairment. Till now, 14 genes have been identified for BBS on different chromosomes, that is, 11q13 (BBS1), 16q21 (BBS2), 3p12 (BBS3), 15q22 (BBS4), 2q31 (BBS5), 20p12 (BBS6), 4q27 (BBS7), 14q32.11 (BBS8), 7p14 (BBS9), 12q21.2 (BBS10), 9q33.1 (BBS11), 4q27 (BBS12), 17q23 (BBS13), and 12q21.3 (BBS14). Genetic and mutational analysis has indicated that a combination of 3 mutant alleles at two loci is necessary for pathogenesity of BBS. Mutations in BBS genes have impact on different pathways. This study is helpful in generating the databank of disease related mutations and in controlling the disease by understanding the pathogenesis of disease.

Key words: Bardet-Biedl Syndrome (BBS), BBS genes, allelic variants.

 

Ansley SJ, Badano JL, Blacque OE, Hill J, Hoskins BE, Leitch CC, Kim JC, Ross J, Eichers ER, Teslovich TM, Mah AK, Johnsen RC, Cavender JC, Lewis RA, Leroux MR, Beales PL and Katsanis N (2003). Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome. Nature 425: 628-633.
http://dx.doi.org/10.1038/nature02030
PMid:14520415
 
Badano JL, Ansley SJ, Leitch CC, Lewis RA, Lupski JR and Katsanis N (2003). Identification of a novel Bardet-Biedl syndrome protein, BBS7 that shares structural features with BBS1 and BBS2. Am. J. Hum. Genet. 72: 650-658.
http://dx.doi.org/10.1086/368204
PMid:12567324 PMCid:PMC1180240
 
Beales PL, Badano JL, Ross AJ, Ansley SJ, Hoskins BE, Kirsten B, Mein CA, Froguel P, Scambler PJ, Lewis RA, Lupski JR and Katsanis N (2003). Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non-mendelian Bardet-Biedl syndrome. Am. J. Hum. Genet., 72: 1187-1199.
http://dx.doi.org/10.1086/375178
PMid:12677556 PMCid:PMC1180271
 
Beales PL, Eleioglu N, Woolf AS, Parker D and Flinter FA (1999). New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey. J. Med. Genet., 36, 437–446.
PMid:10874630 PMCid:PMC1734378
 
Berbari NF, Lewis JS, Bishop GA, Askwith CC, Mykytyn K (2008). Bardet-Biedl syndrome proteins are required for the localization of G protein-coupled receptors to primary cilia. Proc. Nat. Acad. Sci., 105: 4242-4246.
http://dx.doi.org/10.1073/pnas.0711027105
PMid:18334641 PMCid:PMC2393805
 
Bittles AH (2001). Consanguinity and its relevance to clinical genetics. Clin. Genet., 60: 89–98.
http://dx.doi.org/10.1034/j.1399-0004.2001.600201.x
PMid:11553039
 
Blacque OE, Leroux MR (2006). Bardet-Biedl syndrome: an emerging pathomechanism of intracellular transport. Cell. Mol. Life Sci., 63: 2145–2161.
http://dx.doi.org/10.1007/s00018-006-6180-x
PMid:16909204
 
Blacque OE, Leroux MR (2006). Bardet-Biedl syndrome: an emerging pathomechanism of intracellular transport. Cell. Mol. Life Sci., 63: 2145–2161.
http://dx.doi.org/10.1007/s00018-006-6180-x
PMid:16909204
 
Chiang AP, Beck JS, Yen HJ, Tayeh MK, Scheetz TE, Swiderski RE, Nishimura DY, Braun TA, Kim KY, Huang J, Elbedour K, Carmi R, Slusarski DC, Casavant TL, Stone EM, Sheffield VC (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: 6287-6292.
http://dx.doi.org/10.1073/pnas.0600158103
PMid:16606853 PMCid:PMC1458870
 
Chiang A, Nishimura P, Searby D, Elbedour C, Carmi K, Ferguson R, Secrist AL, Braun J, Casavant T, Stone T, Sheffield EM (2004). V. C. Comparative genomic analysis identifies an ADP-ribosylation factor-like gene as the cause of Bardet-Biedl syndrome (BBS3). Am. J. Hum. Genet., 75: 475-484.
http://dx.doi.org/10.1086/423903
PMid:15258860 PMCid:PMC1182025
 
Fan Y, Esmail MA, Ansley SJ, Blacque OE, Boroevich K, Ross AJ, Moore SJ, Badano JL, May-Simera H, Compton DS, Green JS, Lewis RA, van Haelst MM, Parfrey PS, Baillie DL, Beales PL, Katsanis N, Davidson WS, Leroux MR (2004). Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome. Nature Genet., 36: 989-993.
http://dx.doi.org/10.1038/ng1414
PMid:15314642
 
Farag TI, Teebi AS (1988). Bardet-Biedl and Laurence-Moon syndromes in a mixed Arab population. Clin. Genet., 33: 78-82.
http://dx.doi.org/10.1111/j.1399-0004.1988.tb03414.x
PMid:3359670
 
Farag TI, Teebi AS (1989). High incidence of Bardet Biedl syndrome among the Bedouin. (Letter) Clin. Genet., 36: 463-465.
http://dx.doi.org/10.1111/j.1399-0004.1989.tb03378.x
PMid:2591073
 
Forti E, Aksanov O, Birk RZ (2007). Temporal expression pattern of Bardet-Biedl syndrome genes in adipogenesis. Inter. J. Biochem. Cell Biol., 39: 1055–1062.
http://dx.doi.org/10.1016/j.biocel.2007.02.014
PMid:17379567
 
Frosk P, Weiler T, Nylen E, Sudha T, Greenberg CR, Morgan K, Fujiwara TM, Wrogemann K (2002). Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene. Am. J. Hum. Genet., 70: 663-672.
http://dx.doi.org/10.1086/339083
PMid:11822024 PMCid:PMC447621
 
Gerth C, Zawadzki RJ, Werner JS, He’on E (2008). Retinal morphology in patients with BBS1 and BBS10 related Bardet–Biedl Syndrome evaluated by Fourier-domain optical coherence tomography. Vision Res., 48: 392–399.
http://dx.doi.org/10.1016/j.visres.2007.08.024
PMid:17980398 PMCid:PMC2584151
 
Hao L, Scholey JM (2009). Intraflagellar transport at a glance. J. Cell Sci., 122: 889-892.
http://dx.doi.org/10.1242/jcs.023861
PMid:19295122 PMCid:PMC2720924
 
Hjortshoj TD, Gronskov K, Philp AR, Nishimura DY, Adeyemo A, Rotimi CN, Sheffield VC, Rosenberg T, Brondum-Nielsen K (2008). Novel mutations in BBS5 highlight the importance of this gene in non-Caucasian Bardet-Biedl syndrome patients. (Letter) Am. J. Med. Genet., 146A: 517-520.
http://dx.doi.org/10.1002/ajmg.a.32136
PMid:18203199 PMCid:PMC2578871
 
Iannello S, Bosco P, Cavaleri A, Camuto M, Milazzo P, Belfiore F, (2002). A review of the literature of Bardet–Biedl disease and report of three cases associated with metabolic syndrome and diagnosed after the age of fifty. Obesity Rev. 3: 123–135.
http://dx.doi.org/10.1046/j.1467-789X.2002.00055.x
PMid:12120419
 
Ingley E, Williams JH, Walker CE, Tsai S, Colley S, Sayer MS, Tilbrook PA, Sarna M, Beaumont JG, Klinken SP (1999). A novel ADP-ribosylation like factor (ARL-6), interacts with the protein-conducting channel SEC61-beta subunit. FEBS Lett., 459: 69-74.
http://dx.doi.org/10.1016/S0014-5793(99)01188-6
 
Katsanis N, Beales PL, Woods MO, Lewis RA, Green JS, Parfrey PS, Ansley SJ, Davidson WS, Lupski JR (2000). Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome. Nature Genet., 26: 67-70.
http://dx.doi.org/10.1038/79201
PMid:10973251
 
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.
http://dx.doi.org/10.1126/science.1063525
PMid:11567139
 
Katsanis N, Eichers ER, Ansley SJ, Lewis RA, Kayserili H, Hoskins BE, Scambler PJ, Beales PL, Lupski JR (2002). BBS4 is a minor contributor to Bardet-Biedl syndrome and may also participate in triallelic inheritance. Am. J. Hum. Genet., 71: 22-29.
http://dx.doi.org/10.1086/341031
PMid:12016587 PMCid:PMC384990
 
Kim JC, Badano JL, Sibold S, Esmail MA, Hill J, Hoskins BE, Leitch CC, Venner K, Ansley SJ, Ross AJ, Leroux MR, Katsanis N, Beales PL (2004). The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression. Nature Genet., 36: 462-470.
http://dx.doi.org/10.1038/ng1352
PMid:15107855
 
Kim JC, Ou YY, Badano JL, Esmail MA, Leitch CC, Fiedrich E, Beales PL, Archibald JM, Katsanis N, Rattner JB, Leroux MR (2005). MKKS/BBS6, a divergent chaperonin-like protein linked to the obesity disorder Bardet-Biedl syndrome, is a novel centrosomal component required for cytokinesis. J. Cell Sci., 118: 1007-1020.
http://dx.doi.org/10.1242/jcs.01676
PMid:15731008
 
Kudryashova E, Wu J, Havton LA, Spencer MJ (2009). Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a neurogenic component. Hum. Molec. Genet., 18: 1353-1367.
http://dx.doi.org/10.1093/hmg/ddp036
PMid:19155210 PMCid:PMC2722196
 
Laurence JZ, Moon RC (1866). Four cases of retinitis pigmentosa occurring in the same family and accompanied by general imperfection of development. Opthal. Rev., 2: 32–41.
 
Laurier V, Stoetzel C, Muller J, Thibault C, Corbani S, Jalkh N, Salem N, Chouery E, Poch O, Licaire S, Danse JM, Amati-Bonneau P, Bonneau D, Megarbane A, Mandel JL, Dollfus H (2006). Pitfalls of homozygosity mapping: an extended consanguineous Bardet-Biedl syndrome family with two mutant genes (BBS2, BBS10), three mutations, but no triallelism. Europ. J. Hum. Genet., 14: 1195-1203.
http://dx.doi.org/10.1038/sj.ejhg.5201688
PMid:16823392
 
Leitch CC, Zaghloul NA, Davis EE, Stoetzel C, Diaz-Font A, Rix S, Alfadhel M, Lewis RA, Eyaid W, Banin E, Dollfus H, Beales PL, Badano JL, Katsanis N (2008). Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome. Nature Genet., 40: 443-448.
http://dx.doi.org/10.1038/ng0708-927b
http://dx.doi.org/10.1038/ng.97
PMid:18327255
 
Li JB, Gerdes JM, Haycraft CJ, Fan Y, Teslovich TM, May-Simera H, Li H, Blacque OE, Li L, Leitch CC, Lewis RA, Green JS (2004). Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene. Cell 117: 541-552.
http://dx.doi.org/10.1016/S0092-8674(04)00450-7
 
Mykytyn K, Braun T, Carmi R, Haider NB, Searsby CC, Shastri M, Beck G, Wright AF, Iannaccone A, Elbedour K, Riise R, Baldi A, Raas-Rothschild A, Gorman SW, Duhl DM, Jacobson SG, Casavant T, Stone EM, Sheffield VC (2001). Identification of the gene that, when mutated, causes the human obesity syndrome BBS4. Nature Genet., 28: 188-191.
http://dx.doi.org/10.1038/88925
PMid:11381270
 
Mykytyn K, Nishimura DY, Searby CC, Beck G, Bugge K, Haines HL, Cornier AS, Cox GF, Fulton AB, Carmi R, Iannaccone A, Jacobson SG, Weleber RG, Wright AF, Riise R, Hennekam RC, Lüleci G, Berker-Karauzum S, Biesecker LG, Stone EM, Sheffield VC (2003). Evaluation of complex inheritance involving the most common Bardet-Biedl syndrome locus (BBS1). Am. J. Hum. Genet., 72: 429-437.
http://dx.doi.org/10.1086/346172
PMid:12524598 PMCid:PMC379234
 
Mykytyn K, Nishimura DY, Searby CC, Shastri M, Yen H, Beck JS, Braun T, Streb LM, Cornier AS, Cox GF, Fulton AB, Carmi R, Luleci G, Chandrasekharappa SC, Collins FS, Jacobson SG, Heckenlively JR, Weleber RG, Stone EM, Sheffield VC (2002). Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome. Nature Genet., 31: 435-438.
PMid:12118255
 
Nachury MV, Loktev AV, Zhang Q, Westlake CJ, Peranen 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.
http://dx.doi.org/10.1016/j.cell.2007.03.053
PMid:17574030
 
Nishimura DY, Searby CC, Carmi R, Elbedour K, Van Maldergem L, Fulton AB, Lam BL, Powell BR, Swiderski RE, Bugge KE, Haider NB, Kwitek-Black AE, Ying L, Duhl DM, Gorman SW, Heon E, Iannaccone A, Bonneau D, Biesecker LG, Jacobson SG, Stone EM, Sheffield VC (2001). Positional cloning of a novel gene on chromosome 16q causing Bardet-Biedl syndrome (BBS2). Hum. Molec. Genet., 10: 865-874.
http://dx.doi.org/10.1093/hmg/10.8.865
PMid:11285252
 
Nishimura DY, Swiderski RE, Searby CC, Berg EM, Ferguson AL, Hennekam R, Merin S, Weleber RG, Biesecker LG, Stone EM, Sheffield VC (2005). Comparative genomics and gene expression analysis identifies BBS9, a new Bardet-Biedl syndrome gene. Am. J. Hum. Genet., 77: 1021-1033.
http://dx.doi.org/10.1086/498323
PMid:16380913 PMCid:PMC1285160
 
Ou G, Blacque OE, Snow JJ, Leroux MR, Scholey JM (2005). Functional coordination of intraflagellar transport motors. Nature 436, 583-587.
http://dx.doi.org/10.1038/nature03818
PMid:16049494
 
Pawlik B, Mir A, Iqbal H, Lia Y, Nürnberge G, Beckere C, Qamar R, Nürnberga P, Wollnik B (2010). A Novel Familial BBS12 Mutation Associated with a Mild Phenotype: Implications for Clinical and Molecular Diagnostic Strategies. Molecular Syndromology (DOI: 10.1159/000276763).
http://dx.doi.org/10.1159/000276763
 
Ross AJ, May-Simera H, Eichers ER, Kai M, Hill J, Jagger DJ, Leitch CC, Chapple JP, Munro PM, Fisher S, Tan PL, Phillips HM, Leroux MR, Henderson DJ, Murdoch JN, Copp AJ, Eliot MM, Lupski JR, Kemp DT, Dollfus H, Tada M Katsanis N, Forge A, Beales PL, (2005). Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. 37: 1135-1140. Note; Erratum: Nat Genet., 37:1381.
 
Saccone V, Palmieri M, Passamano L, Piluso G, Meroni G, Politano L and Nigro V (2008). Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H. Hum. Mutat., 29: 240-247.
http://dx.doi.org/10.1002/humu.20633
PMid:17994549
 
Seo S, Guo D, Bugge K, Donald A, Rahmouni MK, Sheffield VC (2009). Requirement of Bardet-Biedl Syndrome Proteins for Leptin Receptor Signaling. Human Mole. Genet.
http://dx.doi.org/10.1093/hmg/ddp031
PMid:19150989 PMCid:PMC2655773
 
Slavotinek AM, Stone EM, Mykytyn K, Heckenlively JR, Green JS, Heon E, Musarella MA, Parfrey PS, Sheffield VC, Biesecker LG (2000). Mutations in MKKS cause Bardet-Biedl syndrome. Nature Genet., 26: 15-16.
http://dx.doi.org/10.1038/79116
PMid:10973238
 
Stoetzel C, Laurier V, Davis EE, Muller J, Rix S, Badano JL, Leitch CC, Salem N, Chouery E, Corbani S, Jalk N, Vicaire S, et al., (2006b) BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS locus. Nature Genet., 38: 521-524. Note; Erratum: Nature Genet., 38: 727.
 
Stoetzel C, Laurier V, Faivre L, Mégarbané A, Perrin-Schmitt F, Verloes A, Bonneau D, Mandel JL, Cossee M, Dollfus H (2006a). BBS8 is rarely mutated in a cohort of 128 Bardet-Biedl syndrome families. J. Hum. Genet. 51: 81-84.
http://dx.doi.org/10.1007/s10038-005-0320-2
PMid:16308660
 
Stoetzel C, Muller J, Laurier V, Davis EE, Zaghloul NA, Vicaire S, Jacquelin C, Plewniak F, Leitch CC, Sarda P, Hamel C, Ravel TJ, Lewis RA, Friederich E, Thibault C, Danse JM, Verloes A, Bonneau D, Katsanis N, Poch O, Mandel JL, Dollfus H (2007). Identification of a novel BBS gene (BBS12) highlights the major role of a vertebrate-specific branch of chaperonin-related proteins in Bardet-Biedl syndrome. Am. J. Hum. Genet. 80: 1-11.
http://dx.doi.org/10.1086/510256
PMid:17160889 PMCid:PMC1785304
 
Stoetzel C, Muller J, Laurier V, Davis EE, Zaghloul NA, Vicaire S, Jacquelin C, Plewniak F, Leitch CC, Sarda P, Hamel C, de Ravel TJ (2007). Identification of a novel BBS gene (BBS12) highlights the major role of a vertebrate-specific branch of chaperonin-related proteins in Bardet-Biedl syndrome. Am. J. Hum. Genet. 80: 1-11.
http://dx.doi.org/10.1086/510256
PMid:17160889 PMCid:PMC1785304
 
Stone DL, Slavotinek A, Bouffard GG, Banerjee-Basu S, Baxevanis AD, Barr M, Biesecker LG (2000). Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome. Nature Genet. 25: 79-82.
http://dx.doi.org/10.1038/75637
PMid:10802661
 
Valente EM, Silhavy JL, Brancati F, Barrano G, Krishnaswami SR, Castori M, Lancaster MA, Boltshauser E, Boccone L, Al-Gazali L, Fazzi E, Signorini S, Louie CM, Bellacchio E (2006). International Joubert Syndrome Related Disorders (JSRD) Study Group; Bertini E, Dallapiccola B, Gleeson JG, Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropic forms of Joubert syndrome. Nature Genet. 38: 623-625.
http://dx.doi.org/10.1038/ng1805
PMid:16682970
 
Vernon EG, Malik K, Reynolds P, Powlesland R, Dallosso AR, Jackson S, Henthorn K, Green ED, Brown KW (2003). The parathyroid hormone-responsive B1 gene is interrupted by a t(1;7)(q42; 15) breakpoint associated with Wilms' tumour. Oncogene 22: 1371-1380.
http://dx.doi.org/10.1038/sj.onc.1206332
PMid:12618763
 
Zaghloul NA, Katsanis N (2009). Mechanistic insights into Bardet-Biedl syndrome, a model ciliopathy. J. Clin. Invest. 119(3):428-437.
http://dx.doi.org/10.1172/JCI37041
PMid:19252258 PMCid:PMC2648685
 
Zhenglin Y, Yang Y, Zhao P, Chen K, Chen B, Lin Y, Guo F, Chen Y, Liu X, Lu F, Shi Y, Zhang D, Liao S, Xia Q (2008). A novel mutation in BBS7 gene causes Bardet–Biedl syndrome in a Chinese family. Molecular Vision 14: 2304-2308.

 


APA (2010). Molecular variants of Bardet-Biedl Syndrome. Journal of Cell Biology and Genetics, 1(1), 1 - 11.
Chicago Hina Iqbal, Hussain Mustatab Wahedi, Fauzia Yusuf Hafeez and Asif Mir. "Molecular variants of Bardet-Biedl Syndrome." Journal of Cell Biology and Genetics 1, no. 1 (2010): 1 - 11.
MLA Hina Iqbal, et al. "Molecular variants of Bardet-Biedl Syndrome." Journal of Cell Biology and Genetics 1.1 (2010): 1 - 11.
   
DOI
URL http://academicjournals.org/journal/JCBG/article-abstract/3834F5B822

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