Abstract
Bardet-Biedl syndrome (BBS) is a pleiotropic genetic disorder with the cardinal features of obesity, photoreceptor degeneration, polydactyly, hypogenitalism, renal abnormalities, and developmental delay. Other associated clinical findings in BBS patients include diabetes, hypertension, and congenital heart defects. The clinical diagnosis is based on the presence of at least four of the cardinal symptoms. BBS is recognized to be a genetically heterogeneous autosomal recessive disorder mapping to eight known loci. Positional cloning and candidate gene evaluation have resulted in the identification of six BBS genes. Mutation of one of these genes, BBS6, also causes McKusick-Kaufman syndrome. The BBS6 gene is predicted to code for a protein with sequence similarity to the chaperonin family of proteins. The predicted BBS1, BBS2, BBS4, BBS7, and BBS8 gene products do not seem to be molecular chaperones, on the basis of a lack of sequence similarity to the chaperonin family of proteins. The identification of BBS8 suggests a possible role in cilia function for BBS gene products. It remains to be determined whether the multiple BBS proteins are part of a multisubunit complex or do not directly interact with each other but are part of a common pathway. The study of BBS illustrates the value of using isolated inbred populations for the study of human genetic diseases and suggests strategies for facilitating the study of complex diseases and traits.
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Abbreviations
- BBS:
-
Bardet-Biedl syndrome
- MKS:
-
McKusick-Kaufman syndrome
References
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Acknowledgements
I thank the numerous members of the laboratory who have contributed to this work, including G. Beck, J. Beck, T. Braun, K.E. Bugge, N. Haider, A. Kwitek-Black, K. Mykytyn, D. Nishimura, C.C. Searby, M. Shastri, L.M. Streb, R. Swiderski, H.-J. Yen, and L. Ying. I also thank the following individuals without whom this work would not have been accomplished: Drs. L.G. Biesecker, R. Carmi, T. Casavant, SC Chandrasekharappa, A.S. Cornier, G.F. Cox, D.M. Duhl, K. Elbedour, A.B. Fulton, J.R. Heckenlively, E. Heon, A. Iannaccone, S.G. Jacobson, R. Riise, A. Raas-Rothschild, E.M. Stone, R.G. Weleber, and A.F. Wright.
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This work was supported in part by NIH grants EY11298, HL55006 and HL62178. VCS is an investigator of the Howard Hughes Medical Institute.V.C.S. was the recipient of the Society for Pediatric Research 2003 E. Mead Johnson Award presented at the 2003 Annual Meeting of the Pediatric Academic Societies, Seattle, WA, U.S.A.
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Sheffield, V. Use of Isolated Populations in the Study of a Human Obesity Syndrome, the Bardet-Biedl Syndrome. Pediatr Res 55, 908–911 (2004). https://doi.org/10.1203/01.pdr.0000127013.14444.9c
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DOI: https://doi.org/10.1203/01.pdr.0000127013.14444.9c
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