Bardet-Biedl Syndrome 5

A number sign (#) is used with this entry because Bardet-Biedl syndrome-5 (BBS5) is caused by homozygous mutation in the BBS5 gene (603650) on chromosome 2q31.

Description

BBS5 is a ciliopathy associated with severe and early-onset retinal dystrophy, postaxial polydactyly, obesity, renal dysfunction, hypogonadism, and learning difficulties (summary by Scheidecker et al., 2015). Patients described by Young et al. (1999) and Moore et al. (2005) with mutations in the BBS5 gene did not have polydactyly. The contribution of BBS5 mutations to all cases of BBS has been estimated at 2% (Li et al., 2004) and 0.40% (Zaghloul and Katsanis, 2009).

For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).

Clinical Features

Young et al. (1999) reported that in 5 affected members of a BBS5 kindred, related as sibs or first cousins in 3 sibships and of ages varying from 21 to 31 years, none had polydactyly, but all had brachydactyly and/or syndactyly. All had severe visual impairment with retinal macular changes, and in the 2 males examined, the penis was small.

In a 22-year prospective cohort study of 46 patients from 26 Newfoundland families with BBS, Moore et al. (2005) found that 1 patient who had been diagnosed with Laurence-Moon syndrome (245800) was from a consanguineous family with BBS linked to the BBS5 gene. Another was a compound heterozygote for mutations in the MKKS gene (604896.0007 and 604896.0008) and had been previously reported by Katsanis et al. (2000) as having BBS6 (605231). Moore et al. (2005) concluded that the features in this population did not support the notion that BBS and LMS are distinct.

In 6 patients with molecularly confirmed BBS, including 1 patient with BBS5, Scheidecker et al. (2015) found a cone-rod pattern of dysfunction. Macular dystrophy was present in all patients, usually with central hypofluorescence surrounded by a continuous hyperfluorescent ring on fundus autofluorescence imaging. Optical coherence tomography confirmed loss of outer retinal structure within the atrophic areas.

Mapping

By a genomewide scan of pooled DNA samples using microsatellite markers in a family with BBS, Young et al. (1999) demonstrated that the BBS5 locus maps to 2q31. The 2q31 region is close to the HOXD gene cluster (142987), but refined mapping of the recombinant ancestral chromosome excluded all genes within that cluster as candidates for BBS5.

Molecular Genetics

In a patient from the consanguineous Newfoundland family with BBS described by Young et al. (1999), Li et al. (2004) detected a homozygous A-to-G transition at the +3 position of the exon 6 splice donor site of the BBS5 gene (603650.0001). An affected sib was also homozygous for the mutation; both parents were heterozygous, and 4 unaffected sibs were either heterozygous or homozygous wildtype. Li et al. (2004) identified pathogenic mutations in the BBS5 gene in several other patients with BBS. Li et al. (2004) also presented evidence that BBS5 may interact genetically with BBS1 (209901).

Hjortshoj et al. (2008) identified mutations in the BBS5 gene (603650.0005 and 603650.0006) in 5 patients from 2 unrelated non-Caucasian families with BBS.