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Bardet-Biedl syndrome

Disease Pathophysiology Research Report

2025-12-15
Falcon MONDO:0015229 Model: Edison Scientific Literature 17 citations

Disease Pathophysiology Research Report

Target Disease

  • Disease Name: Bardet–Biedl Syndrome (BBS)
  • MONDO ID: MONDO:0012746
  • Category: Genetic (autosomal recessive ciliopathy)

Pathophysiology Description

Bardet–Biedl syndrome is a prototypical non-motile ciliopathy caused by defects in proteins that localize predominantly to the primary cilium and its basal body/transition zone, leading to impaired ciliary compartmentalization and trafficking of membrane and signaling proteins across tissues including retina, kidney, and hypothalamus (energy balance) (melluso2023bardetbiedlsyndromecurrent pages 1-3). Mechanistically, BBS proteins assemble into the octameric BBSome with support from a dedicated chaperonin-like complex (BBS6/MKKS, BBS10, BBS12) and interface with intraflagellar transport (IFT) to regulate ciliary entry/retention and retrieval of G-protein–coupled receptors (GPCRs) and other membrane cargos (melluso2023bardetbiedlsyndromecurrent pages 1-3, melluso2023bardetbiedlsyndromecurrent pages 17-18). In photoreceptors, disruption of BBSome/IFT-mediated trafficking across the connecting cilium (“ciliary gate”) causes mislocalization of outer-segment proteins and triggers cell death and retinal degeneration (delvallee2023retinaldegenerationanimal pages 2-4). The multisystem phenotype reflects shared dependence on ciliary signaling and compartmentalization across organs (melluso2023bardetbiedlsyndromecurrent pages 1-3).

Direct quotes highlighting core mechanisms: - “The BBSome is defined as an octameric complex (BBS1/2/4/5/7/8/9/BBIP1) whose assembly requires chaperonin-like proteins (BBS6, BBS10, BBS12)… A functional link to the BBS3 GTPase enables intraflagellar transport (IFT)” (DOI: 10.2147/TCRM.S338653) (melluso2023bardetbiedlsyndromecurrent pages 1-3). - In photoreceptors “more than 1000 rhodopsin molecules [are] transiting per second… Defective IFT or BBSome-mediated trafficking causes abnormal protein trafficking across the [connecting cilium], provoking proapoptotic reactions and photoreceptor degeneration” (DOI: 10.1101/cshperspect.a041303) (delvallee2023retinaldegenerationanimal pages 2-4).

1. Core Pathophysiology

2. Key Molecular Players

3. Biological Processes (GO terms; disrupted)

4. Cellular Components (GO/CL/UBERON)

5. Disease Progression

6. Phenotypic Manifestations (HP terms)

Tissue-Specific Mechanisms

Recent Developments and Latest Research (prioritized 2023–2024)

Note: Although additional 2023–2024 mechanistic advances (e.g., BBSome ubiquitylation, TOM1L2-mediated ubiquitin recognition, refined IFT-B interfaces, EV/ectocytosis, and cAMP microdomains in cilia) are widely reported in the field, they were not present in the retrieved evidence excerpts and thus are not detailed here.

Current Applications and Real-World Implementations

Expert Opinions and Authoritative Analyses

Relevant Statistics and Data from Recent Studies

Gene/Protein Annotations (selected)

Ontology Mappings

Evidence Items

1) Melluso A, et al. Bardet–Biedl Syndrome: Current Perspectives and Clinical Outlook. Therapeutics and Clinical Risk Management. Jan 2023. DOI: 10.2147/TCRM.S338653; URL: https://doi.org/10.2147/TCRM.S338653 (melluso2023bardetbiedlsyndromecurrent pages 1-3, melluso2023bardetbiedlsyndromecurrent pages 12-14, melluso2023bardetbiedlsyndromecurrent pages 17-18, melluso2023bardetbiedlsyndromecurrent pages 14-15). 2) Delvallée C, Dollfus H. Retinal Degeneration Animal Models in Bardet–Biedl Syndrome and Related Ciliopathies. Cold Spring Harb Perspect Med. Jan 2023. DOI: 10.1101/cshperspect.a041303; URL: https://doi.org/10.1101/cshperspect.a041303 (delvallee2023retinaldegenerationanimal pages 2-4). 3) Lazareva J, Brady SM, Yanovski JA. An evaluation of setmelanotide injection for chronic weight management in adult and pediatric patients with obesity due to Bardet–Biedl syndrome. Expert Opin Pharmacother. Apr 2023. DOI: 10.1080/14656566.2023.2199152; URL: https://doi.org/10.1080/14656566.2023.2199152 (lazareva2023anevaluationof pages 8-11, lazareva2023anevaluationof pages 16-18).

Limitations: Additional 2024 advances (e.g., revised European consensus diagnostic criteria; detailed molecular updates on ubiquitylation and ciliary ubiquitin readers; EV/ectocytosis and cAMP microdomains) are recognized in the field but were not included in the retrieved excerpts; thus, mechanistic claims here are limited to the cited 2023 sources and their referenced evidence (melluso2023bardetbiedlsyndromecurrent pages 17-18).

References

  1. (melluso2023bardetbiedlsyndromecurrent pages 1-3): Andrea Melluso, Floriana Secondulfo, Giovanna Capolongo, Giovambattista Capasso, and Miriam Zacchia. Bardet-biedl syndrome: current perspectives and clinical outlook. Therapeutics and Clinical Risk Management, 19:115-132, Jan 2023. URL: https://doi.org/10.2147/tcrm.s338653, doi:10.2147/tcrm.s338653. This article has 91 citations and is from a peer-reviewed journal.

  2. (melluso2023bardetbiedlsyndromecurrent pages 17-18): Andrea Melluso, Floriana Secondulfo, Giovanna Capolongo, Giovambattista Capasso, and Miriam Zacchia. Bardet-biedl syndrome: current perspectives and clinical outlook. Therapeutics and Clinical Risk Management, 19:115-132, Jan 2023. URL: https://doi.org/10.2147/tcrm.s338653, doi:10.2147/tcrm.s338653. This article has 91 citations and is from a peer-reviewed journal.

  3. (delvallee2023retinaldegenerationanimal pages 2-4): Clarisse Delvallée and Hélène Dollfus. Retinal degeneration animal models in bardet-biedl syndrome and related ciliopathies. Cold Spring Harbor perspectives in medicine, 13 1:a041303, Jan 2023. URL: https://doi.org/10.1101/cshperspect.a041303, doi:10.1101/cshperspect.a041303. This article has 12 citations and is from a peer-reviewed journal.

  4. (melluso2023bardetbiedlsyndromecurrent pages 14-15): Andrea Melluso, Floriana Secondulfo, Giovanna Capolongo, Giovambattista Capasso, and Miriam Zacchia. Bardet-biedl syndrome: current perspectives and clinical outlook. Therapeutics and Clinical Risk Management, 19:115-132, Jan 2023. URL: https://doi.org/10.2147/tcrm.s338653, doi:10.2147/tcrm.s338653. This article has 91 citations and is from a peer-reviewed journal.

  5. (lazareva2023anevaluationof pages 16-18): Julia Lazareva, Sheila M. Brady, and Jack A. Yanovski. An evaluation of setmelanotide injection for chronic weight management in adult and pediatric patients with obesity due to bardet–biedl syndrome. Expert Opinion on Pharmacotherapy, 24:667-674, Apr 2023. URL: https://doi.org/10.1080/14656566.2023.2199152, doi:10.1080/14656566.2023.2199152. This article has 13 citations and is from a peer-reviewed journal.

  6. (melluso2023bardetbiedlsyndromecurrent pages 12-14): Andrea Melluso, Floriana Secondulfo, Giovanna Capolongo, Giovambattista Capasso, and Miriam Zacchia. Bardet-biedl syndrome: current perspectives and clinical outlook. Therapeutics and Clinical Risk Management, 19:115-132, Jan 2023. URL: https://doi.org/10.2147/tcrm.s338653, doi:10.2147/tcrm.s338653. This article has 91 citations and is from a peer-reviewed journal.

  7. (lazareva2023anevaluationof pages 8-11): Julia Lazareva, Sheila M. Brady, and Jack A. Yanovski. An evaluation of setmelanotide injection for chronic weight management in adult and pediatric patients with obesity due to bardet–biedl syndrome. Expert Opinion on Pharmacotherapy, 24:667-674, Apr 2023. URL: https://doi.org/10.1080/14656566.2023.2199152, doi:10.1080/14656566.2023.2199152. This article has 13 citations and is from a peer-reviewed journal.