title: Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder.
abstract: Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by multiple clinical features that include pigmentary retinal dystrophy, polydactyly, obesity, developmental delay, and renal defects. BBS is considered an autosomal recessive disorder, and recent positional cloning efforts have identified two BBS genes (BBS2 and BBS6). We screened our cohort of 163 BBS families for mutations in both BBS2 and BBS6 and report the presence of three mutant alleles in affected individuals in four pedigrees. In addition, we detected unaffected individuals in two pedigrees who carry two BBS2 mutations but not a BBS6 mutation. We therefore propose that BBS may not be a single-gene recessive disease but a complex trait requiring three mutant alleles to manifest the phenotype. This triallelic model of disease transmission may be important in the study of both Mendelian and multifactorial disorders.
authors.affiliation: Department of Molecular and Human Genetics, The Texas Children's Hospital, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: N
authors.initials: N
authors.lastname: Katsanis
authors.forename: S J
authors.initials: SJ
authors.lastname: Ansley
authors.forename: J L
authors.initials: JL
authors.lastname: Badano
authors.forename: E R
authors.initials: ER
authors.lastname: Eichers
authors.forename: R A
authors.initials: RA
authors.lastname: Lewis
authors.forename: B E
authors.initials: BE
authors.lastname: Hoskins
authors.forename: P J
authors.initials: PJ
authors.lastname: Scambler
authors.forename: W S
authors.initials: WS
authors.lastname: Davidson
authors.forename: P L
authors.initials: PL
authors.lastname: Beales
authors.forename: J R
authors.initials: JR
authors.lastname: Lupski
mesh_terms: D000483:Alleles; D020788:Bardet-Biedl Syndrome / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005808:Genes, Recessive; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D020412:Multifactorial Inheritance; D009154:Mutation; D016366:Open Reading Frames; D010375:Pedigree