title: Identification of the gene that, when mutated, causes the human obesity syndrome BBS4.
abstract: Bardet-Biedl syndrome (BBS, MIM 209900) is a heterogeneous autosomal recessive disorder characterized by obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation, and hypogenitalism. The disorder is also associated with diabetes mellitus, hypertension, and congenital heart disease. Six distinct BBS loci map to 11q13 (BBS1), 16q21 (BBS2), 3p13-p12 (BBS3), 15q22.3-q23 (BBS4), 2q31 (BBS5), and 20p12 (BBS6). Although BBS is rare in the general population (<1/100,000), there is considerable interest in identifying the genes causing BBS because components of the phenotype, such as obesity and diabetes, are common. We and others have demonstrated that BBS6 is caused by mutations in the gene MKKS (refs. 12,13), mutation of which also causes McKusick-Kaufman syndrome (hydrometrocolpos, post-axial polydactyly, and congenital heart defects). MKKS has sequence homology to the alpha subunit of a prokaryotic chaperonin in the thermosome Thermoplasma acidophilum. We recently identified a novel gene that causes BBS2. The BBS2 protein has no significant similarity to other chaperonins or known proteins. Here we report the positional cloning and identification of mutations in BBS patients in a novel gene designated BBS4.
authors.affiliation: Department of Pediatrics, Division of Medical Genetics and the Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa, 52242, USA.
authors.forename: K
authors.initials: K
authors.lastname: Mykytyn
authors.forename: T
authors.initials: T
authors.lastname: Braun
authors.forename: R
authors.initials: R
authors.lastname: Carmi
authors.forename: N B
authors.initials: NB
authors.lastname: Haider
authors.forename: C C
authors.initials: CC
authors.lastname: Searby
authors.forename: M
authors.initials: M
authors.lastname: Shastri
authors.forename: G
authors.initials: G
authors.lastname: Beck
authors.forename: A F
authors.initials: AF
authors.lastname: Wright
authors.forename: A
authors.initials: A
authors.lastname: Iannaccone
authors.forename: K
authors.initials: K
authors.lastname: Elbedour
authors.forename: R
authors.initials: R
authors.lastname: Riise
authors.forename: A
authors.initials: A
authors.lastname: Baldi
authors.forename: A
authors.initials: A
authors.lastname: Raas-Rothschild
authors.forename: S W
authors.initials: SW
authors.lastname: Gorman
authors.forename: D M
authors.initials: DM
authors.lastname: Duhl
authors.forename: S G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: T
authors.initials: T
authors.lastname: Casavant
authors.forename: E M
authors.initials: EM
authors.lastname: Stone
authors.forename: V C
authors.initials: VC
authors.lastname: Sheffield
mesh_terms: D020788:Bardet-Biedl Syndrome / Q000235:genetics*; D003001:Cloning, Molecular; D003241:Consanguinity; D020224:Expressed Sequence Tags; D006801:Humans; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D011506:Proteins / Q000235:genetics*
chemical_list: C429655:BBS4 protein, human; D008869:Microtubule-Associated Proteins; D011506:Proteins