NPOG 2009 Abstract template

Foredragsholder / Presenter

Navn / Name: Ruth Riise

Institusjon/Institution:

Avdeling / Department: Medisinsk Genetikk, Rikshospitalet, Oslo

Gate / Street: (priv) Storhamargt. 126

Post nr. / zip code: N-2315 Hamar

Land / Country: Norway

ABSTRACT

BARDET-BIEDL (LMBB) SYNDROME, A MODEL CILIOPATHY.

Bardet-Biedl syndrome is an autosomal recessive inherited multiorgan disorder with both developmental and progressive degenerative defects. Characteristic features are rod/cone retinal dystrophy, obesity, polydactyly, hypogenitalism and renal disorder. The retinal dystrophy appears in childhood with progression to legal blindness in the teenages. Onset of obesity is at age 2 years with progression to severe overweight. Polydactyly is of postaxial type and is found in 75% of patients. Hypogenitalism is mostly diagnosed in men. Renal disorder has been the most frequent cause of death. Other features associated with Bardet-Biedl syndrome include mental retardation, neurological impairment, hearing loss, diabetes mellitus, cardiovascular and hepatic disorders, and Hirschsprung disease.

Twelve causative genes have been identified (BBS1-12). In addition the genes for Meckel-Gruber Syndrome and Nephronophthisis can be involved. Mutations in BBS10 and BBS1 are the most frequent. But still are 21% of the genes unknown.

The first evidence that Bardet-Biedl syndrome is caused by a defect in ciliary function was obtained from the identification of BBS8, where a patient with a mutation in this gene also had Situs Inversus, a common outcome of defects in the nodal cilium. It was shown that all BBS proteins were localized either to centrosomes, basal bodies or cilia including the connecting cilium between the inner- and outer segment of the photoreceptors.

Defects that impact function of cilia have been shown in a number of other diseases including Leber congenital amaurosis, Alström syndrome, Joubert syndrome, Senior-Løken syndrome, Meckel-Gruber syndrome, Orofaciodigital syndrome and probably also Usher syndrome.

The molecular mechanisms underlying the various features in Bardet-Biedl syndrome have recently been studied and an understanding of the molecular defects has provided insight into defects in other ciliopathies.

The role of ciliopathy in each of the cardinal features in Bardet-Biedl syndrome is discussed.