1.1 Name of the disease (synonyms)
Bardet–Biedl syndrome (BBS); Laurence–Moon–Bardet–Biedl syndrome; Laurence–Moon–Biedl syndrome.
Other synonyms include ARL6-related Bardet–Biedl syndrome, BBS1-related Bardet–Biedl syndrome, BBS2-related Bardet–Biedl syndrome, BBS4-related Bardet–Biedl syndrome, BBS5-related Bardet–Biedl syndrome, BBS7-related Bardet–Biedl syndrome, BBS9-related Bardet–Biedl syndrome, BBS10-related Bardet–Biedl syndrome, BBS12-related Bardet–Biedl syndrome, CEP290-related Bardet–Biedl syndrome, MKKS-related Bardet–Biedl syndrome, MKS1-related Bardet–Biedl syndrome, TRIM32-related Bardet–Biedl syndrome, TTC8-related Bardet–Biedl syndrome.
1.2 OMIM# of the disease
1.3 Name of the analysed genes or DNA/chromosome segments
1.4 OMIM# of the gene(s)
BBS1 209901; BBS2 606151; BBS3/ARL6 608845; BBS4 600374; BBS5 603650; BBS6/MKKS 604896; BBS7 607590; BBS8/TTC8 608132; BBS9 607968; BBS10 610148; BBS11/TRIM32 602290; BBS12 610683; BBS13/MKS1 609883; BBS14/CEP290 610142.
1.5 Mutational spectrum
BBS1 has a common mutation, p.Met390Arg (p.M390R), which accounted for 18% of the total number of mutated alleles in 259 individuals with BBS.1 A frameshift mutation, C91fsX95, is commonly found in 48% of the patients with BBS10 mutations, but mutation hotspots are otherwise rare throughout the BBS genes.
1.6 Analytical methods
Genomic sequencing of the coding regions of the commonest causative genes has been most frequently employed to search for BBS mutations. Gene-sequencing panels have more recently become available (see Section 2.3). Large deletions and genomic rearrangements are rare and array comparative genomic hybridization and karyotyping are not routinely performed.2
1.7 Analytical validation
Sequence alterations that could be mutations are bidirectionally sequenced and can be re-sequenced in normal, ethnically matched controls to exclude polymorphisms.
1.8 Estimated frequency of the disease (incidence at birth (‘birth prevalence') or population prevalence)
1.9 If applicable, prevalence in the ethnic group of investigated person
BBS has a higher prevalence in populations with a high incidence of consanguinity or that are subject to possible founder effects. In the Bedouin from the mixed Arab population of Kuwait, prevalence ranged from 1 in 13500 to 1 in 36000.7, 8 In New Foundland, the frequency of BBS was estimated to be 1 in 17500.9
1.10 Diagnostic setting
Mutation testing in BBS is used mainly to confirm a suspected clinical diagnosis. A list of laboratories that perform clinical and research testing of the BBS genes can be found on the GeneTests website (http://www.ncbi.nlm.nih.gov/sites/GeneTests/ ?db=GeneTests). Predictive testing without disease manifestations is less common. Prenatal testing is available for families with known mutations.