Details of Disease

General Information of Disease (ID: DISTBNZW)

• Disease Name: Bardet biedl syndrome
• Synonyms: Bardet-Biedl syndrome; BBS
• Disease Class: 5A61: Pituitary hypofunction
• Definition: A ciliopathy with multisystem involvement. It is invariantly characterized by rod-cone dystrophy, and at least three additional non-ocular features such as intellectual disability, obesity, polydactyly, hypogonadism, or renal anomalies as primary manifestations. In the absence of one of these four primary clinical features, the diagnosis of BBS is made when at least two secondary features are observed, including hepatic fibrosis, diabetes mellitus, reproductive and developmental abnormalities, growth retardation, speech delays, or cardiovascular problems
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DISCPWH9: Autosomal recessive disease
  DIS10G4I: Ciliopathy
  DISTBNZW: Bardet biedl syndrome
• ICD Code: ICD-11: ICD-11: 5A61.0
• Disease Identifiers:
  MONDO ID: MONDO_0015229
  MESH ID: D020788
  UMLS CUI: C0752166
  MedGen ID: 156019
  Orphanet ID: 110
  SNOMED CT ID: 5619004

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Setmelanotide	DMPVRN9	Approved	NA	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 56 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
WDPCP	OT0HF6PJ	Supportive	Autosomal recessive	[2]
SCLT1	OT2ZSSP4	Limited	Autosomal recessive	[7]
ARL6	OTLV3SBS	Supportive	Autosomal recessive	[2]
BBIP1	OTGMET92	Supportive	Autosomal recessive	[8]
BBS1	OTXSXB1K	Supportive	Autosomal recessive	[2]
BBS10	OTL1TTWX	Supportive	Autosomal recessive	[9]
BBS12	OT43DTAV	Supportive	Autosomal recessive	[2]
BBS2	OTPF9JIB	Supportive	Autosomal recessive	[2]
BBS4	OT0D3JC0	Supportive	Autosomal recessive	[2]
BBS5	OTFWF9N1	Supportive	Autosomal recessive	[2]
BBS7	OTELYWDQ	Supportive	Autosomal recessive	[2]
BBS9	OT23V9YF	Supportive	Autosomal recessive	[2]
CEP19	OTL2WXOR	Supportive	Autosomal recessive	[10]
CEP290	OTVN52VH	Supportive	Autosomal recessive	[2]
IFT172	OT12DW08	Supportive	Autosomal recessive	[11]
IFT27	OT3NY6O6	Supportive	Autosomal recessive	[12]
IFT74	OTZBFEDD	Supportive	Autosomal recessive	[13]
LZTFL1	OTIEIOEW	Supportive	Autosomal recessive	[14]
MKKS	OTLF5T11	Supportive	Autosomal recessive	[2]
MKS1	OT83W5PB	Supportive	Autosomal recessive	[15]
NPHP1	OTZHCFFQ	Supportive	Autosomal recessive	[16]
SCAPER	OT7S3B3P	Supportive	Autosomal recessive	[17]
SDCCAG8	OTV2ZGV9	Supportive	Autosomal recessive	[18]
TRIM32	OTJOV0PG	Supportive	Autosomal recessive	[2]
TTC8	OTBGDZBD	Supportive	Autosomal recessive	[2]
ALMS1	OTW66JKS	Strong	Biomarker	[19]
ASTN2	OTF0W2FJ	Strong	CausalMutation	[20]
AZIN1	OTX5W77I	Strong	Biomarker	[21]
CCDC28B	OT1HFHN2	Strong	Biomarker	[22]
CEP131	OT6PF80T	Strong	Biomarker	[21]
CEP164	OTLNRPAR	Strong	Genetic Variation	[23]
FEM1B	OTFE2ELA	Strong	Biomarker	[24]
FEZ1	OTWCXPRE	Strong	Biomarker	[25]
GLIS2	OTOUUV1X	Strong	Biomarker	[26]
INPP5E	OTJF2AZ9	Strong	Genetic Variation	[27]
INVS	OT8KPESR	Strong	Genetic Variation	[28]
IQCB1	OTYQ28V9	Strong	Biomarker	[29]
KIF2A	OT2WQ6QD	Strong	Biomarker	[30]
KIFC3	OTOPD4QO	Strong	Genetic Variation	[31]
MAGEL2	OTXEL4R7	Strong	Biomarker	[25]
MARVELD2	OTKB96L5	Strong	Biomarker	[32]
MYO3B	OTVD4TNG	Strong	Genetic Variation	[33]
MYO7A	OTBZSPEL	Strong	Genetic Variation	[34]
MYO9A	OTE3XHKY	Strong	Altered Expression	[34]
NDN	OTYBYJ82	Strong	Biomarker	[25]
NMB	OT4NLN6H	Strong	Biomarker	[35]
PCM1	OTFM133C	Strong	Biomarker	[36]
PDE6B	OTOJMB1V	Strong	Genetic Variation	[37]
PIGX	OTUN0WC4	Strong	CausalMutation	[10]
PLLP	OTFGCB9U	Strong	Genetic Variation	[38]
RAB8A	OTPB54Y3	Strong	Biomarker	[29]
RFX1	OTZUDMPR	Strong	Altered Expression	[39]
RIN2	OTCY73U9	Strong	Genetic Variation	[40]
STOML3	OTLQGALK	Strong	Genetic Variation	[41]
SULT1A4	OTHJ8WWV	Strong	Genetic Variation	[6]
TMEM67	OTME92T5	Strong	Biomarker	[15]

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CEP290	TT3XBOV	Supportive	Autosomal recessive	[2]
CEP290	TT3XBOV	Strong	Genetic Variation	[3]
NPY2R	TTJ6WK9	Strong	Biomarker	[4]
RCVRN	TTDQTEY	Strong	Biomarker	[5]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
SULT1A3	DEP7E8X	Strong	Genetic Variation	[6]

References

• [1] ClinicalTrials.gov (NCT03746522) Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alstrom Syndrome (AS) Patients With Moderate to Severe Obesity. U.S. National Institutes of Health.
• [2] Bardet-Biedl Syndrome Overview. 2003 Jul 14 [updated 2023 Mar 23]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [3] Ciliary genes arl13b, ahi1 and cc2d2a differentially modify expression of visual acuity phenotypes but do not enhance retinal degeneration due to mutation of cep290 in zebrafish.PLoS One. 2019 Apr 10;14(4):e0213960. doi: 10.1371/journal.pone.0213960. eCollection 2019.
• [4] Neuropeptide Y family receptors traffic via the Bardet-Biedl syndrome pathway to signal in neuronal primary cilia.Cell Rep. 2013 Dec 12;5(5):1316-29. doi: 10.1016/j.celrep.2013.11.011. Epub 2013 Dec 5.
• [5] Evaluation of the human gene encoding recoverin in patients with retinitis pigmentosa or an allied disease.Invest Ophthalmol Vis Sci. 1997 Mar;38(3):704-9.
• [6] Altered myogenesis and premature senescence underlie human TRIM32-related myopathy.Acta Neuropathol Commun. 2019 Mar 1;7(1):30. doi: 10.1186/s40478-019-0683-9.
• [7] Bardet-Biedl syndrome in two unrelated patients with identical compound heterozygous SCLT1 mutations. CEN Case Rep. 2020 Aug;9(3):260-265. doi: 10.1007/s13730-020-00472-y. Epub 2020 Apr 6.
• [8] Exome sequencing of Bardet-Biedl syndrome patient identifies a null mutation in the BBSome subunit BBIP1 (BBS18). J Med Genet. 2014 Feb;51(2):132-6. doi: 10.1136/jmedgenet-2013-101785. Epub 2013 Sep 11.
• [9] Novel homozygous mutations in the genes ARL6 and BBS10 underlying Bardet-Biedl syndrome. Gene. 2013 Feb 15;515(1):84-8. doi: 10.1016/j.gene.2012.11.023. Epub 2012 Dec 6.
• [10] Homozygous mutation in CEP19, a gene mutated in morbid obesity, in Bardet-Biedl syndrome with predominant postaxial polydactyly. J Med Genet. 2018 Mar;55(3):189-197. doi: 10.1136/jmedgenet-2017-104758. Epub 2017 Nov 10.
• [11] Mutations in IFT172 cause isolated retinal degeneration and Bardet-Biedl syndrome. Hum Mol Genet. 2015 Jan 1;24(1):230-42. doi: 10.1093/hmg/ddu441. Epub 2014 Aug 28.
• [12] IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet-Biedl syndrome. Hum Mol Genet. 2014 Jun 15;23(12):3307-15. doi: 10.1093/hmg/ddu044. Epub 2014 Jan 31.
• [13] Copy-Number Variation Contributes to the Mutational Load of Bardet-Biedl Syndrome. Am J Hum Genet. 2016 Aug 4;99(2):318-36. doi: 10.1016/j.ajhg.2015.04.023.
• [14] Exome sequencing identifies mutations in LZTFL1, a BBSome and smoothened trafficking regulator, in a family with Bardet--Biedl syndrome with situs inversus and insertional polydactyly. J Med Genet. 2012 May;49(5):317-21. doi: 10.1136/jmedgenet-2012-100737. Epub 2012 Apr 17.
• [15] Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome. Nat Genet. 2008 Apr;40(4):443-8. doi: 10.1038/ng.97. Epub 2008 Mar 9.
• [16] Recurrent CNVs and SNVs at the NPHP1 locus contribute pathogenic alleles to Bardet-Biedl syndrome. Am J Hum Genet. 2014 May 1;94(5):745-54. doi: 10.1016/j.ajhg.2014.03.017. Epub 2014 Apr 17.
• [17] SCAPER localizes to primary cilia and its mutation affects cilia length, causing Bardet-Biedl syndrome. Eur J Hum Genet. 2019 Jun;27(6):928-940. doi: 10.1038/s41431-019-0347-z. Epub 2019 Feb 5.
• [18] Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy. Nat Genet. 2010 Oct;42(10):840-50. doi: 10.1038/ng.662. Epub 2010 Sep 12.
• [19] Functional analysis by minigene assay of putative splicing variants found in Bardet-Biedl syndrome patients.J Cell Mol Med. 2017 Oct;21(10):2268-2275. doi: 10.1111/jcmm.13147. Epub 2017 May 13.
• [20] Scapuloperoneal muscular dystrophy phenotype due to TRIM32-sarcotubular myopathy in South Dakota Hutterite.Neuromuscul Disord. 2013 Feb;23(2):133-8. doi: 10.1016/j.nmd.2012.09.010. Epub 2012 Nov 9.
• [21] The centriolar satellite protein AZI1 interacts with BBS4 and regulates ciliary trafficking of the BBSome.PLoS Genet. 2014 Feb 13;10(2):e1004083. doi: 10.1371/journal.pgen.1004083. eCollection 2014 Feb.
• [22] Kinesin 1 regulates cilia length through an interaction with the Bardet-Biedl syndrome related protein CCDC28B.Sci Rep. 2018 Feb 14;8(1):3019. doi: 10.1038/s41598-018-21329-6.
• [23] Genetic and clinical characterization of Pakistani families with Bardet-Biedl syndrome extends the genetic and phenotypic spectrum. Sci Rep. 2016 Oct 6;6:34764. doi: 10.1038/srep34764.
• [24] Rapid communication: the human FEM1B gene maps to chromosome 15q22 and is excluded as the gene for Bardet-Biedl syndrome, type 4.Am J Med Sci. 2000 Apr;319(4):268-70. doi: 10.1097/00000441-200004000-00014.
• [25] Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth.Hum Mol Genet. 2005 Mar 1;14(5):627-37. doi: 10.1093/hmg/ddi059. Epub 2005 Jan 13.
• [26] Interaction with the Bardet-Biedl gene product TRIM32/BBS11 modifies the half-life and localization of Glis2/NPHP7.J Biol Chem. 2014 Mar 21;289(12):8390-401. doi: 10.1074/jbc.M113.534024. Epub 2014 Feb 5.
• [27] INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse. Nat Genet. 2009 Sep;41(9):1027-31. doi: 10.1038/ng.427. Epub 2009 Aug 9.
• [28] Active transport and diffusion barriers restrict Joubert Syndrome-associated ARL13B/ARL-13 to an Inv-like ciliary membrane subdomain.PLoS Genet. 2013;9(12):e1003977. doi: 10.1371/journal.pgen.1003977. Epub 2013 Dec 5.
• [29] Nephrocystin proteins NPHP5 and Cep290 regulate BBSome integrity, ciliary trafficking and cargo delivery.Hum Mol Genet. 2015 Apr 15;24(8):2185-200. doi: 10.1093/hmg/ddu738. Epub 2014 Dec 30.
• [30] Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport.PLoS Genet. 2016 Dec 8;12(12):e1006469. doi: 10.1371/journal.pgen.1006469. eCollection 2016 Dec.
• [31] Cloning of a novel C-terminal kinesin (KIFC3) that maps to human chromosome 16q13-q21 and thus is a candidate gene for Bardet-Biedl syndrome.Genomics. 1998 Sep 1;52(2):219-22. doi: 10.1006/geno.1998.5431.
• [32] Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential assembly of stable bardet-biedl syndrome protein complex, the BBSome.J Biol Chem. 2012 Jun 8;287(24):20625-35. doi: 10.1074/jbc.M112.341487. Epub 2012 Apr 12.
• [33] A class III myosin expressed in the retina is a potential candidate for Bardet-Biedl syndrome.Genomics. 2002 May;79(5):621-4. doi: 10.1006/geno.2002.6749.
• [34] The cloning and developmental expression of unconventional myosin IXA (MYO9A) a gene in the Bardet-Biedl syndrome (BBS4) region at chromosome 15q22-q23.Genomics. 1999 Jul 15;59(2):150-60. doi: 10.1006/geno.1999.5867.
• [35] Significant association between a silent polymorphism in the neuromedin B gene and body weight in German children and adolescents.Acta Diabetol. 2000;37(2):93-101. doi: 10.1007/s005920070026.
• [36] The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression.Nat Genet. 2004 May;36(5):462-70. doi: 10.1038/ng1352. Epub 2004 Apr 25.
• [37] Multiple genetic mutations implicate spectrum of phenotypes in Bardet-Biedl syndrome.Gene. 2020 Jan 30;725:144164. doi: 10.1016/j.gene.2019.144164. Epub 2019 Oct 19.
• [38] Plasmolipin: genomic structure, chromosomal localization, protein expression pattern, and putative association with Bardet-Biedl syndrome.Mamm Genome. 2001 Dec;12(12):933-7. doi: 10.1007/s00335-001-3035-5.
• [39] Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.Nature. 2003 Oct 9;425(6958):628-33. doi: 10.1038/nature02030. Epub 2003 Sep 21.
• [40] RIN2 and BBS7 variants as cause of a coincidental syndrome.Eur J Med Genet. 2020 Mar;63(3):103755. doi: 10.1016/j.ejmg.2019.103755. Epub 2019 Sep 12.
• [41] Loss of Bardet Biedl syndrome proteins causes defects in peripheral sensory innervation and function.Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17524-9. doi: 10.1073/pnas.0706618104. Epub 2007 Oct 24.