In search of triallelism in Bardet-Biedl syndrome.

Eur J Hum Genet 2012 Apr 22;20(4):420-7. Epub 2012 Feb 22.

Developmental Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Bardet-Biedl syndrome (BBS) is a model disease for ciliopathy in humans. The remarkable genetic heterogeneity that characterizes this disease is consistent with accumulating data on the interaction between the proteins encoded by the 14 BBS genes identified to date. Previous reports suggested that such interaction may also extend to instances of oligogenic inheritance in the form of triallelism which defies the long held view of BBS as an autosomal recessive disease. In order to investigate the magnitude of triallelism in BBS, we conducted a comprehensive analysis of all 14 BBS genes as well as the CCDC28B-modifier gene in a cohort of 29 BBS families, most of which are multiplex. Two in trans mutations in a BBS gene were identified in each of these families for a total of 20 mutations including 12 that are novel. In no instance did we observe two mutations in unaffected members of a given family, or observe the presence of a third allele that convincingly acted as a modifier of penetrance and supported the triallelic model of BBS. In addition to presenting a comprehensive genotype/phenotype overview of a large set of BBS mutations, including the occurrence of nonsyndromic retinitis pigmentosa in a family with a novel BBS9 mutation, our study argues in favor of straightforward autosomal recessive BBS in most cases.

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http://dx.doi.org/10.1038/ejhg.2011.205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306854PMC
April 2012
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