title: Testing for triallelism: analysis of six BBS genes in a Bardet-Biedl syndrome family cohort.
abstract: The phenotype of Bardet-Biedl syndrome (BBS) is defined by the association of retinitis pigmentosa, obesity, polydactyly, hypogenitalism, renal disease and cognitive impairement. The significant genetic heterogeneity of this condition is supported by the identification, to date, of eight genes (BBS1-8) implied with cilia assembly or function. Triallelic inheritance has recently been suggested on the basis of the identification of three mutated alleles in two different genes for the same patient. In a cohort of 27 families, six BBS genes (namely BBS1, BBS2, BBS4, BBS6, BBS7 and BBS8) have been studied. Mutations were identified in 14 families. Two mutations within the same gene have been identified in seven families. BBS1 is most frequently implied with the common M390R substitution at the homozygous state (n=2), or associated with another mutation at BBS1 (n=3). Compound heterozygous mutations have been found in BBS2 (one family) and BBS6 (one family). In seven other families, only one heterozygous mutation has been identified (once in BBS1, twice for BBS2 and three times in BBS6). Although our study did not reveal any families with bona fide mutations in two BBS genes, consistent with a triallelic hypothesis, we have found an excess of heterozygous single mutations. This study underlines the genetic heterogeneity of the BBS and the involvement of possibly unidentified genes.
authors.affiliation: Laboratoire de diagnostic génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Haifa
authors.initials: H
authors.lastname: Hichri
authors.forename: Corinne
authors.initials: C
authors.lastname: Stoetzel
authors.forename: Virginie
authors.initials: V
authors.lastname: Laurier
authors.forename: Solenne
authors.initials: S
authors.lastname: Caron
authors.forename: Sabine
authors.initials: S
authors.lastname: Sigaudy
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarda
authors.forename: Christian
authors.initials: C
authors.lastname: Hamel
authors.forename: Dominique
authors.initials: D
authors.lastname: Martin-Coignard
authors.forename: Morin
authors.initials: M
authors.lastname: Gilles
authors.forename: Bruno
authors.initials: B
authors.lastname: Leheup
authors.forename: Mureille
authors.initials: M
authors.lastname: Holder
authors.forename: Josseline
authors.initials: J
authors.lastname: Kaplan
authors.forename: Pierre
authors.initials: P
authors.lastname: Bitoun
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonneau
authors.forename: Fabienne
authors.initials: F
authors.lastname: Perrin-Schmitt
authors.forename: Christian
authors.initials: C
authors.lastname: Brandt
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Besancon
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mandel
authors.forename: Mireille
authors.initials: M
authors.lastname: Cossée
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D000595:Amino Acid Sequence; D020788:Bardet-Biedl Syndrome / Q000235:genetics*; D015331:Cohort Studies; D003598:Cytoskeletal Proteins; D005260:Female; D005602:France; D006580:Genetic Carrier Screening; D018740:Genetic Heterogeneity; D005820:Genetic Testing / Q000379:methods; D056385:Group II Chaperonins; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D011506:Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C429655:BBS4 protein, human; C464790:Bbs1 protein, human; C473309:Bbs2 protein, human; C473308:Bbs7 protein, human; D003598:Cytoskeletal Proteins; C414726:MKKS protein, human; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D011506:Proteins; D056385:Group II Chaperonins