title: Evaluation of complex inheritance involving the most common Bardet-Biedl syndrome locus (BBS1).
abstract: Bardet-Biedl syndrome (BBS) is a genetic disorder with the primary features of obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation, and hypogenitalism. Patients with BBS are also at increased risk for diabetes mellitus, hypertension, and congenital heart disease. BBS is known to map to at least six loci: 11q13 (BBS1), 16q21 (BBS2), 3p13-p12 (BBS3), 15q22.3-q23 (BBS4), 2q31 (BBS5), and 20p12 (BBS6). Although these loci were all mapped on the basis of an autosomal recessive mode of inheritance, it has recently been suggested-on the basis of mutation analysis of the identified BBS2, BBS4, and BBS6 genes-that BBS displays a complex mode of inheritance in which, in some families, three mutations at two loci are necessary to manifest the disease phenotype. We recently identified BBS1, the gene most commonly involved in Bardet-Biedl syndrome. The identification of this gene allows for further evaluation of complex inheritance. In the present study we evaluate the involvement of the BBS1 gene in a cohort of 129 probands with BBS and report 10 novel BBS1 mutations. We demonstrate that a common BBS1 missense mutation accounts for approximately 80% of all BBS1 mutations and is found on a similar genetic background across populations. We show that the BBS1 gene is highly conserved between mice and humans. Finally, we demonstrate that BBS1 is inherited in an autosomal recessive manner and is rarely, if ever, involved in complex inheritance.
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, and Howard Hughes Medical Institute, University of Iowa, Iowa City, IA, 52242, USA.
authors.forename: Kirk
authors.initials: K
authors.lastname: Mykytyn
authors.forename: Darryl Y
authors.initials: DY
authors.lastname: Nishimura
authors.forename: Charles C
authors.initials: CC
authors.lastname: Searby
authors.forename: Gretel
authors.initials: G
authors.lastname: Beck
authors.forename: Kevin
authors.initials: K
authors.lastname: Bugge
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Haines
authors.forename: Alberto S
authors.initials: AS
authors.lastname: Cornier
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Cox
authors.forename: Anne B
authors.initials: AB
authors.lastname: Fulton
authors.forename: Rivka
authors.initials: R
authors.lastname: Carmi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Iannaccone
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: Richard G
authors.initials: RG
authors.lastname: Weleber
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
authors.forename: Ruth
authors.initials: R
authors.lastname: Riise
authors.forename: Raoul C M
authors.initials: RC
authors.lastname: Hennekam
authors.forename: Güven
authors.initials: G
authors.lastname: Lüleci
authors.forename: Sibel
authors.initials: S
authors.lastname: Berker-Karauzum
authors.forename: Leslie G
authors.initials: LG
authors.lastname: Biesecker
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020788:Bardet-Biedl Syndrome / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D015331:Cohort Studies; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005808:Genes, Recessive; D006239:Haplotypes; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010802:Phylogeny; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: C464790:Bbs1 protein, human; D008869:Microtubule-Associated Proteins; D011506:Proteins