Bardet-Biedl syndrome (BBS) is a recessive genetic disease causing multiple organ anomalies. Most patients carry mutations in genes encoding for the subunits of the BBSome, an octameric ciliary transport complex, or accessory proteins involved in the BBSome assembly or function. BBS proteins have been extensively studied using in vitro, cellular, and animal models. However, the molecular functions of particular BBS proteins and the etiology of the BBS symptoms are still largely elusive. In this study, we applied a meta-analysis approach to study the genotype-phenotype association in humans using our database of all reported BBS patients. The analysis revealed that the identity of the causative gene and the character of the mutation partially predict the clinical outcome of the disease. Besides their potential use for clinical prognosis, our analysis revealed functional differences of particular BBS genes in humans. Core BBSome subunits BBS2, BBS7, and BBS9 manifest as more critical for the function and development of kidneys than peripheral subunits BBS1, BBS4, and BBS8/TTC8, suggesting that incomplete BBSome retains residual function at least in the kidney.
- MeSH
- ADP-ribosylační faktory genetika MeSH
- Bardetův-Biedlův syndrom diagnóza genetika MeSH
- fenotyp * MeSH
- genetická predispozice k nemoci * MeSH
- genetické asociační studie * metody MeSH
- genotyp * MeSH
- kognitivní dysfunkce genetika MeSH
- ledviny abnormality MeSH
- lidé MeSH
- mutace MeSH
- nemoci ledvin vrozené genetika MeSH
- penetrance MeSH
- proteiny genetika MeSH
- vrozené vady genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
