title: Clinical evidence of decreased olfaction in Bardet-Biedl syndrome caused by a deletion in the BBS4 gene.
abstract: Recent discoveries have lead to the hypothesis that ciliary dysfunction is a mechanism underlying the pathogenesis of Bardet-Biedl syndrome (BBS). Here, we describe two individuals with decreased olfaction who are members of an extended family affected with BBS caused by a homozygous deletion (c.77-220del) in the BBS4 gene. These findings correlate with the evidence that several BBS proteins, including BBS4, are expressed in the olfactory epithelium (OE). Although the prevalence and the spectrum of impaired olfaction in BBS are not known, the causal relationship of the BBS4 deletion in this family and the decreased olfaction is corroborated by evidence that Bbs2 and Bbs4 knockout mice have severe olfaction deficits and that also patients with BBS caused by mutations in other BBS genes can have impaired olfaction. This finding broadens the spectrum of clinical manifestations associated with BBS, confirms the role of BBS4 in olfaction, and lends support to the hypothesis that ciliary dysfunction is an important aspect of BBS pathogenesis.
authors.affiliation: Hamilton Eye Institute, Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, USA. iannacca@utmem.edu
authors.forename: Alessandro
authors.initials: A
authors.lastname: Iannaccone
authors.forename: Kirk
authors.initials: K
authors.lastname: Mykytyn
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Persico
authors.forename: Charles C
authors.initials: CC
authors.lastname: Searby
authors.forename: Alfonso
authors.initials: A
authors.lastname: Baldi
authors.forename: Monica M
authors.initials: MM
authors.lastname: Jablonski
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
mesh_terms: D000328:Adult; D020788:Bardet-Biedl Syndrome / Q000235:genetics* / Q000503:physiopathology; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins; D011506:Proteins / Q000235:genetics*; D012903:Smell / Q000502:physiology*
chemical_list: C429655:BBS4 protein, human; D008869:Microtubule-Associated Proteins; D011506:Proteins