title: Bardet-Biedl syndrome in Denmark--report of 13 novel sequence variations in six genes.
abstract: Bardet-Biedl syndrome (BBS) is an autosomal recessive disease characterized by retinal dystrophy, polydactyly, obesity, learning disabilities, renal involvement, and male hypogenitalism. BBS is genetically heterogeneous with mutations of 14 genes, accounting for approximately 70% of cases. Triallelic inheritance has been suggested in about 5% of cases. Forty-nine unrelated BBS patients were screened for mutations by DHPLC analysis in BBS1, BBS2, BBS4, BBS6/MKKS, BBS10, and BBS12. The selected genes either account for more than 5% of the mutational load or are commonly reported in triallelic inheritance. Eight patients with only one or no BBS mutation were further investigated by single nucleotide polymorphism (SNP) analysis. In total, mutations were detected in 44 patients. Twenty percent had two mutations in BBS1, 18% in BBS2, 4% in BBS9, 43% in BBS10, and 2% in BBS12. Five patients were heterozygous for a sequence variation in BBS6/MKKS. We found eight patients with three sequence variations in two genes, which could be explained by triallelic inheritance, by the prevalence of heterozygous carriers or the third sequence variations representing rare polymorphisms. All changes found in a second BBS gene were amino acid substitutions. Genotype-phenotype correlations suggest a milder phenotype for BBS1 compared to BBS2 and BBS10, which we ascribe to the hypomorphic p.Met390Arg-mutation.
authors.affiliation: The Kennedy Center, GI. Landevej 7, Glostrup, Denmark. tid@kennedy.dk
authors.forename: Tina Duelund
authors.initials: TD
authors.lastname: Hjortshøj
authors.forename: Karen
authors.initials: K
authors.lastname: Grønskov
authors.forename: Alisdair R
authors.initials: AR
authors.lastname: Philp
authors.forename: Darryl Y
authors.initials: DY
authors.lastname: Nishimura
authors.forename: Ruth
authors.initials: R
authors.lastname: Riise
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenberg
authors.forename: Karen
authors.initials: K
authors.lastname: Brøndum-Nielsen
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D020788:Bardet-Biedl Syndrome / Q000235:genetics*; D001483:Base Sequence; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D003718:Denmark; D019143:Evolution, Molecular; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D056385:Group II Chaperonins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D056385:Group II Chaperonins