bardet biedl syndrome


Summary: An autosomal recessive disorder characterized by RETINITIS PIGMENTOSA; POLYDACTYLY; OBESITY; MENTAL RETARDATION; hypogenitalism; renal dysplasia; and short stature. This syndrome has been distinguished as a separate entity from LAURENCE-MOON SYNDROME. (From J Med Genet 1997 Feb;34(2):92-8)

Top Publications

  1. Mykytyn K, Mullins R, Andrews M, Chiang A, Swiderski R, Yang B, et al. Bardet-Biedl syndrome type 4 (BBS4)-null mice implicate Bbs4 in flagella formation but not global cilia assembly. Proc Natl Acad Sci U S A. 2004;101:8664-9 pubmed
    ..To further evaluate an association between cilia and BBS, we performed homology comparisons of BBS proteins in model organisms and find that BBS proteins are specifically conserved in ciliated organisms. ..
  2. Katsanis N, Ansley S, Badano J, Eichers E, Lewis R, Hoskins B, et al. Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder. Science. 2001;293:2256-9 pubmed
    ..This triallelic model of disease transmission may be important in the study of both Mendelian and multifactorial disorders. ..
  3. Blacque O, Leroux M. Bardet-Biedl syndrome: an emerging pathomechanism of intracellular transport. Cell Mol Life Sci. 2006;63:2145-61 pubmed
    ..From these discoveries, a common theme has emerged, namely that the primary function of BBS proteins may be to mediate and regulate microtubule-based intracellular transport processes. ..
  4. Mykytyn K, Braun T, Carmi R, Haider N, Searby C, Shastri M, et al. Identification of the gene that, when mutated, causes the human obesity syndrome BBS4. Nat Genet. 2001;28:188-91 pubmed
    ..The BBS2 protein has no significant similarity to other chaperonins or known proteins. Here we report the positional cloning and identification of mutations in BBS patients in a novel gene designated BBS4. ..
  5. Zaghloul N, Katsanis N. Mechanistic insights into Bardet-Biedl syndrome, a model ciliopathy. J Clin Invest. 2009;119:428-37 pubmed publisher
  6. Leroux M. Taking vesicular transport to the cilium. Cell. 2007;129:1041-3 pubmed
  7. Stoetzel C, Laurier V, Faivre L, Megarbane A, Perrin Schmitt F, Verloes A, et al. BBS8 is rarely mutated in a cohort of 128 Bardet-Biedl syndrome families. J Hum Genet. 2006;51:81-4 pubmed
    ..Two of the three families have homozygous mutations and one has a heterozygous mutation. Mutations in BBS8 probably account for only a minority of BBS families (2%), underlining the difficulty of genotyping heterogeneous conditions. ..
  8. Davis R, Swiderski R, Rahmouni K, Nishimura D, Mullins R, Agassandian K, et al. A knockin mouse model of the Bardet-Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity. Proc Natl Acad Sci U S A. 2007;104:19422-7 pubmed
  9. Yen H, Tayeh M, Mullins R, Stone E, Sheffield V, Slusarski D. Bardet-Biedl syndrome genes are important in retrograde intracellular trafficking and Kupffer's vesicle cilia function. Hum Mol Genet. 2006;15:667-77 pubmed
    ..These studies are the first to comprehensively compare the diverse group of BBS genes in parallel and demonstrate a common role in intracellular trafficking, indicating that BBS proteins are involved in general organelle trafficking. ..

More Information


  1. Laurier V, Stoetzel C, Muller J, Thibault C, Corbani S, Jalkh N, et al. Pitfalls of homozygosity mapping: an extended consanguineous Bardet-Biedl syndrome family with two mutant genes (BBS2, BBS10), three mutations, but no triallelism. Eur J Hum Genet. 2006;14:1195-203 pubmed
  2. Nishimura D, Fath M, Mullins R, Searby C, Andrews M, Davis R, et al. Bbs2-null mice have neurosensory deficits, a defect in social dominance, and retinopathy associated with mislocalization of rhodopsin. Proc Natl Acad Sci U S A. 2004;101:16588-93 pubmed
    ..The evaluation of Bbs2(-/-) mice indicates additional phenotypes that should be evaluated in human patients, including deficits in social interaction and infertility. ..
  3. Nishimura D, Swiderski R, Searby C, Berg E, Ferguson A, Hennekam R, et al. Comparative genomics and gene expression analysis identifies BBS9, a new Bardet-Biedl syndrome gene. Am J Hum Genet. 2005;77:1021-33 pubmed
    ..This type of mutation is likely to be underreported because of the difficulty of deletion detection in the heterozygous state by the mutation screening methods that are used in many studies. ..
  4. Moore S, Green J, Fan Y, Bhogal A, Dicks E, Fernandez B, et al. Clinical and genetic epidemiology of Bardet-Biedl syndrome in Newfoundland: a 22-year prospective, population-based, cohort study. Am J Med Genet A. 2005;132A:352-60 pubmed
    ..The features in this population do not support the notion that BBS and LMS are distinct. The lack of a genotype-phenotype correlation implies that BBS proteins interact and are necessary for the development of many organs. ..
  5. Kobayashi T, Hori Y, Ueda N, Kajiho H, Muraoka S, Shima F, et al. Biochemical characterization of missense mutations in the Arf/Arl-family small GTPase Arl6 causing Bardet-Biedl syndrome. Biochem Biophys Res Commun. 2009;381:439-42 pubmed publisher
    ..These findings implicate that Arl6 mutants are destabilized and eliminated by the proteasome in cells, probably due to the altered nucleotide-binding properties. ..
  6. Nishimura D, Searby C, Carmi R, Elbedour K, Van Maldergem L, Fulton A, et al. Positional cloning of a novel gene on chromosome 16q causing Bardet-Biedl syndrome (BBS2). Hum Mol Genet. 2001;10:865-74 pubmed
    ..In addition, mutations were found in three of 18 unrelated BBS probands from small nuclear families. ..
  7. Benzinou M, Walley A, Lobbens S, Charles M, Jouret B, Fumeron F, et al. Bardet-Biedl syndrome gene variants are associated with both childhood and adult common obesity in French Caucasians. Diabetes. 2006;55:2876-82 pubmed
    ..g., dyslipidemia, hyperglycemia), a complication previously described in BBS patients. In summary, our preliminary data suggest that variations at BBS genes are associated with risk of common obesity. ..
  8. Kulaga H, Leitch C, Eichers E, Badano J, Lesemann A, Hoskins B, et al. Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouse. Nat Genet. 2004;36:994-8 pubmed
    ..Our data indicate that BBS proteins have a role in the microtubule organization of mammalian ciliated cells and that anosmia might be a useful determinant of other pleiotropic disorders with a suspected ciliary involvement. ..
  9. Tayeh M, Yen H, Beck J, Searby C, Westfall T, Griesbach H, et al. Genetic interaction between Bardet-Biedl syndrome genes and implications for limb patterning. Hum Mol Genet. 2008;17:1956-67 pubmed publisher
    ..This study reveals an in vivo requirement for BBS function in limb bud patterning. Our results provide important new insights into the mechanism and biological significance of BBS. ..
  10. Slavotinek A, Stone E, Mykytyn K, Heckenlively J, Green J, Heon E, et al. Mutations in MKKS cause Bardet-Biedl syndrome. Nat Genet. 2000;26:15-6 pubmed
    ..Both parents and the maternal grandfather were heterozygous for the deletions. Genotyping with markers from the MKKS region confirmed homozygosity at 20p12 in both affected individuals. ..
  11. Nachury M, Loktev A, Zhang Q, Westlake C, Peranen J, Merdes A, et al. A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell. 2007;129:1201-13 pubmed
    ..Conversely, preventing Rab8(GTP) production blocks ciliation in cells and yields characteristic BBS phenotypes in zebrafish. Our data reveal that BBS may be caused by defects in vesicular transport to the cilium. ..
  12. Tan P, Barr T, Inglis P, Mitsuma N, Huang S, Garcia Gonzalez M, et al. Loss of Bardet Biedl syndrome proteins causes defects in peripheral sensory innervation and function. Proc Natl Acad Sci U S A. 2007;104:17524-9 pubmed
    ..Our findings suggest a hitherto unrecognized, but essential, role for mammalian basal body proteins in the acquisition of mechano- and thermosensory stimuli and highlight potentially clinical features of ciliopathies in humans. ..
  13. Smaoui N, Chaabouni M, Sergeev Y, Kallel H, Li S, Mahfoudh N, et al. Screening of the eight BBS genes in Tunisian families: no evidence of triallelism. Invest Ophthalmol Vis Sci. 2006;47:3487-95 pubmed
  14. Abd El Barr M, Sykoudis K, Andrabi S, Eichers E, Pennesi M, Tan P, et al. Impaired photoreceptor protein transport and synaptic transmission in a mouse model of Bardet-Biedl syndrome. Vision Res. 2007;47:3394-407 pubmed
    ..Additionally, we show defects in synaptic transmission from the photoreceptors to secondary neurons of the visual system, demonstrating multiple functions for BBS4 in photoreceptors. ..
  15. Badano J, Ansley S, Leitch C, Lewis R, Lupski J, Katsanis N. Identification of a novel Bardet-Biedl syndrome protein, BBS7, that shares structural features with BBS1 and BBS2. Am J Hum Genet. 2003;72:650-8 pubmed
  16. Beales P. Lifting the lid on Pandora's box: the Bardet-Biedl syndrome. Curr Opin Genet Dev. 2005;15:315-23 pubmed
    ..In the next few years, these pathways will be revealed, and their impact on the development of systems as diverse as the cardiovascular, neurological, endocrinological and skeletal will be realized. ..
  17. Fath M, Mullins R, Searby C, Nishimura D, Wei J, Rahmouni K, et al. Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome. Hum Mol Genet. 2005;14:1109-18 pubmed
    ..These observations suggest that the complete absence of MKKS leads to BBS while the MKS phenotype is likely to be due to specific mutations. ..
  18. Singla V, Reiter J. The primary cilium as the cell's antenna: signaling at a sensory organelle. Science. 2006;313:629-33 pubmed
  19. Chiang A, Nishimura D, Searby C, Elbedour K, Carmi R, Ferguson A, et al. Comparative genomic analysis identifies an ADP-ribosylation factor-like gene as the cause of Bardet-Biedl syndrome (BBS3). Am J Hum Genet. 2004;75:475-84 pubmed
    ..These data illustrate the power of comparative genomic analysis for the study of human disease and identifies a novel BBS gene. ..
  20. Heon E, Westall C, Carmi R, Elbedour K, Panton C, Mackeen L, et al. Ocular phenotypes of three genetic variants of Bardet-Biedl syndrome. Am J Med Genet A. 2005;132A:283-7 pubmed
    ..RP was severe and early in all cases. Myopia was associated with BBS3 and BBS4, but not BBS2. One patient with Bardet-Biedl syndrome also had iris and chorioretinal colobomata, features suggestive of Biemond syndrome. ..
  21. Marshall W. What is the function of centrioles?. J Cell Biochem. 2007;100:916-22 pubmed
  22. Kim J, Badano J, Sibold S, Esmail M, Hill J, Hoskins B, et al. The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression. Nat Genet. 2004;36:462-70 pubmed
  23. Berbari N, Lewis J, Bishop G, Askwith C, Mykytyn K. Bardet-Biedl syndrome proteins are required for the localization of G protein-coupled receptors to primary cilia. Proc Natl Acad Sci U S A. 2008;105:4242-6 pubmed publisher
    ..Our results also provide a potential molecular mechanism to link cilia defects with obesity. ..
  24. Shah A, Farmen S, Moninger T, Businga T, Andrews M, Bugge K, et al. Loss of Bardet-Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia. Proc Natl Acad Sci U S A. 2008;105:3380-5 pubmed publisher
    ..These results emphasize the role of BBS proteins in both the structure and function of motile cilia. They also invite additional scrutiny of motile cilia dysfunction in patients with this disease. ..
  25. Hjortshøj T, Grønskov K, Philp A, Nishimura D, Adeyemo A, Rotimi C, et al. Novel mutations in BBS5 highlight the importance of this gene in non-Caucasian Bardet-Biedl syndrome patients. Am J Med Genet A. 2008;146A:517-20 pubmed publisher
  26. Chiang A, Beck J, Yen H, Tayeh M, Scheetz T, Swiderski R, et al. Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11). Proc Natl Acad Sci U S A. 2006;103:6287-92 pubmed
  27. Swiderski R, Nishimura D, Mullins R, Olvera M, Ross J, Huang J, et al. Gene expression analysis of photoreceptor cell loss in bbs4-knockout mice reveals an early stress gene response and photoreceptor cell damage. Invest Ophthalmol Vis Sci. 2007;48:3329-40 pubmed
    ..The molecular and morphologic changes observed in young BBS animal model eyes implies that BBS proteins play a critical, early role in establishing the correct structure and function of photoreceptors. ..
  28. Stoetzel C, Muller J, Laurier V, Davis E, Zaghloul N, Vicaire S, et al. 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. 2007;80:1-11 pubmed
  29. Loktev A, Zhang Q, Beck J, Searby C, Scheetz T, Bazan J, et al. A BBSome subunit links ciliogenesis, microtubule stability, and acetylation. Dev Cell. 2008;15:854-65 pubmed publisher
    ..BBSome-bound BBIP10 may therefore function to couple acetylation of axonemal microtubules and ciliary membrane growth. ..
  30. Badano J, Leitch C, Ansley S, May Simera H, Lawson S, Lewis R, et al. Dissection of epistasis in oligogenic Bardet-Biedl syndrome. Nature. 2006;439:326-30 pubmed
    ..Our data demonstrate how the combined use of biochemical, genetic and in vivo tools can facilitate the dissection of epistatic phenomena, and enhance our appreciation of the genetic basis of phenotypic variability. ..
  31. Tobin J, Beales P. Bardet-Biedl syndrome: beyond the cilium. Pediatr Nephrol. 2007;22:926-36 pubmed
    ..Here we review the recent developments in this emerging field, with the emphasis on the renal component of the syndrome and potential future directions. ..
  32. Fan Y, Esmail M, Ansley S, Blacque O, Boroevich K, Ross A, et al. Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome. Nat Genet. 2004;36:989-93 pubmed
    ..These findings implicate a small GTP-binding protein in ciliary transport and the pathogenesis of a pleiotropic disorder. ..
  33. Kim J, Ou Y, Badano J, Esmail M, Leitch C, Fiedrich E, et al. 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. 2005;118:1007-20 pubmed
    ..Our findings provide the first insight into the nature and cellular function of BBS6, and shed light on the potential causes of several ailments, including obesity, retinal degeneration, kidney dysfunction and congenital heart disease. ..
  34. Tobin J, Di Franco M, Eichers E, May Simera H, Garcia M, Yan J, et al. Inhibition of neural crest migration underlies craniofacial dysmorphology and Hirschsprung's disease in Bardet-Biedl syndrome. Proc Natl Acad Sci U S A. 2008;105:6714-9 pubmed publisher
    ..Moreover, this is a previously undescribed method of using characterization of facial dysmorphology as a basis for investigating the pathomechanism of CF development in dysmorphic syndromes...
  35. Li J, Gerdes J, Haycraft C, Fan Y, Teslovich T, May Simera H, et al. Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene. Cell. 2004;117:541-52 pubmed
    ..We show that this novel protein localizes to basal bodies in mouse and C. elegans, is under the regulatory control of daf-19, and is necessary for the generation of both cilia and flagella...
  36. Hjortshøj T, Grønskov K, Brøndum Nielsen K, Rosenberg T. A novel founder BBS1 mutation explains a unique high prevalence of Bardet-Biedl syndrome in the Faroe Islands. Br J Ophthalmol. 2009;93:409-13 pubmed publisher
    ..The aim of the study was to investigate the genetic background of Bardet-Biedl syndrome in the Faroe Island. It was hypothesised that a common genetic background for the syndrome would be found...
  37. Stoetzel C, Laurier V, Davis E, Muller J, Rix S, Badano J, et al. BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS locus. Nat Genet. 2006;38:521-4 pubmed
    ..In zebrafish, mild suppression of bbs10 exacerbated the phenotypes of other bbs morphants. ..
  38. Ross A, May Simera H, Eichers E, Kai M, Hill J, Jagger D, et al. Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nat Genet. 2005;37:1135-40 pubmed
    ..We also show that Vangl2 localizes to the basal body and axoneme of ciliated cells, a pattern reminiscent of that of the BBS proteins. These data suggest that cilia are intrinsically involved in PCP processes. ..
  39. Rahmouni K, Fath M, Seo S, Thedens D, Berry C, Weiss R, et al. Leptin resistance contributes to obesity and hypertension in mouse models of Bardet-Biedl syndrome. J Clin Invest. 2008;118:1458-67 pubmed publisher
    ..Furthermore, we found that BBS mice had a decreased hypothalamic expression of proopiomelanocortin, which suggests that BBS genes play an important role in maintaining leptin sensitivity in proopiomelanocortin neurons. ..
  40. Mykytyn K, Nishimura D, Searby C, Shastri M, Yen H, Beck J, et al. Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome. Nat Genet. 2002;31:435-8 pubmed
    ..Here we report the identification of the gene BBS1 and show that a missense mutation of this gene is a frequent cause of BBS. In addition, we provide data showing that this common mutation is not involved in triallelic inheritance. ..
  41. Quinlan R, Tobin J, Beales P. Modeling ciliopathies: Primary cilia in development and disease. Curr Top Dev Biol. 2008;84:249-310 pubmed publisher
    ..Herein, we describe the wealth of information derived from the study of the ciliopathies and their animal models. ..
  42. Katsanis N, Beales P, Woods M, Lewis R, Green J, Parfrey P, et al. Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome. Nat Genet. 2000;26:67-70 pubmed
    ..Our data suggest that a complete loss of function of the MKKS product, and thus an inability to fold a range of target proteins, is responsible for the clinical manifestations of BBS. ..
  43. Leitch C, Zaghloul N, Davis E, Stoetzel C, Diaz Font A, Rix S, et al. Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome. Nat Genet. 2008;40:443-8 pubmed publisher
    ..These data extend the genetic stratification of ciliopathies and suggest that BBS and MKS, although distinct clinically, are allelic forms of the same molecular spectrum...
  44. Ansley S, Badano J, Blacque O, Hill J, Hoskins B, Leitch C, et al. Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome. Nature. 2003;425:628-33 pubmed
  45. Teerlink C, Bernhisel R, Cannon Albright L, Rollins M. A population-based description of familial clustering of Hirschsprung disease. J Pediatr Surg. 2018;53:1355-1359 pubmed publisher
    ..This population-based survey of HSCR provides confirmation of a genetic contribution to HSCR disease and presents unbiased risk estimates that may have clinical value in predicting recurrence. Prognosis study, level II. ..
  46. Rooryck C, Lacombe D. [Bardet-Biedl syndrome]. Ann Endocrinol (Paris). 2008;69:463-71 pubmed publisher
    ..Retinal dystrophy leading to progressive vision loss, moderate mental retardation, and obesity will affect social life of these patients. ..
  47. Mykytyn K, Nishimura D, Searby C, Beck G, Bugge K, Haines H, et al. Evaluation of complex inheritance involving the most common Bardet-Biedl syndrome locus (BBS1). Am J Hum Genet. 2003;72:429-37 pubmed
    ..We show that the BBS1 gene is highly conserved between mice and humans. Finally, we demonstrate that BBS1 is inherited in an autosomal recessive manner and is rarely, if ever, involved in complex inheritance. ..
  48. Hostelley T, Lodh S, Zaghloul N. Whole organism transcriptome analysis of zebrafish models of Bardet-Biedl Syndrome and Alström Syndrome provides mechanistic insight into shared and divergent phenotypes. BMC Genomics. 2016;17:318 pubmed publisher
    ..These findings provide important novel insight into shared and divergent phenotypes between two similar but distinct genetic syndromes. ..
  49. Fieggen K, Milligan C, Henderson B, Esterhuizen A. Bardet Biedl syndrome in South Africa: A single founder mutation. S Afr Med J. 2016;106:S72-4 pubmed publisher
    b>Bardet Biedl syndrome (BBS) is a multisystem disorder characterised by obesity, polydactyly, intellectual disability and loss of vision due to a progressive retinopathy...
  50. Dilan T, Singh R, Saravanan T, Moye A, Goldberg A, Stoilov P, et al. Bardet-Biedl syndrome-8 (BBS8) protein is crucial for the development of outer segments in photoreceptor neurons. Hum Mol Genet. 2018;27:283-294 pubmed publisher
    ..The findings from our study also imply that early targeting of both rods and cones in BBS8 patients is crucial for successful restoration of vision. ..
  51. Hjortshøj T, Grønskov K, Rosenberg T, Brøndum Nielsen K, Olsen J. Risk for cancer in patients with Bardet-Biedl syndrome and their relatives. Am J Med Genet A. 2007;143A:1699-702 pubmed
    ..Among the relatives, 30 cancers were observed, with 45.2 expected. No renal cancers were observed in the two groups. These data do not support the suggested increased risk for renal cancer in relatives of patients with BBS. ..
  52. Jacoby M, Cox J, Gayral S, Hampshire D, Ayub M, Blockmans M, et al. INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse. Nat Genet. 2009;41:1027-31 pubmed publisher
    ..Together, our results show that INPP5E plays an essential role in the primary cilium by controlling ciliary growth factor and PI3K signaling and stability, and highlight the consequences of INPP5E dysfunction. ..
  53. Williams C, Uytingco C, Green W, McIntyre J, Ukhanov K, Zimmerman A, et al. Gene Therapeutic Reversal of Peripheral Olfactory Impairment in Bardet-Biedl Syndrome. Mol Ther. 2017;25:904-916 pubmed publisher