aetiology

Last reviewed 01/2018

• Bardet-Biedl syndrome is a genetic condition that is occurs more commonly in inbred populations and as a result of consanguineous relationships
  • there are eleven gene loci that have been identified as being significant aetiological factors in the development of the syndrome. The Bardet-Biedl syndrome gene loci (BBS) are numbered 1-11 and they appear to encode proteins involved with cilia function, microtubule organisation, cell transport and cell division
  • the most commonly identified gene loci are BBS1 and BBS 10 accounting for 23-56% and 20% of cases respectively. The next most common are BBS2 and BBS6 accounting for 8-16% and 4-5% respectively. The remaining gene loci contribute less than 4% each and it is likely that other gene loci are yet to be discovered. (1)
  • mode of inheritance of this syndrome follows a roughly autosomal recessive pattern, although recent research suggests a triallelic mode of inheritance. (2)
  • in some pedigrees there are individuals who are homozygous at one BBS gene loci and do not exhibit the phenotype. In addition to this there are pedigrees in which there are three mutations; with the individual being homozygous one BBS gene loci and heterozygous at another. These individuals do display the full genetic phenotype. It is therefore clear that the inheritance of BBS does not follow a simple Mendelian inheritance pattern. (3)

Reference:

• (1) O. E. Blacque and M. R. Leroux, " Bardet-Biedl syndrome: an emerging pathomechanism of intracellular transport" Cell. Mol. Life Sci. 63 (2006) 2145-2161
• (2) Beales, P.L., Badano, J. L., Ross, A. J., Ansley, S. J., Hoskins, B. E., Kirsten, B., Mein, C. A., Froguel, P., Scambler, P. J.,Lewis, R. A., Lupski, J. R. and Katsanis, N. (2003) Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non-Mendelian Bardet-Biedl syndrome. Am. J.Hum. Genet. 72, 1187-1199.
• (3) Hichri, H., Stoetzel, C., Laurier, V., Caron, S., Sigaudy, S., Sarda, P., Hamel C, Martin-Coignard, D., Gilles, M., Leheup, B. et al. (2005) Testing for triallelism: analysis of six BBS genes in a Bardet-Biedl syndrome cohort. Eur. J. Hum. Genet.13, 607-616