title: Mutations in chaperonin-like BBS genes are a major contributor to disease development in a multiethnic Bardet-Biedl syndrome patient population.
abstract: BACKGROUND
  Bardet-Biedl syndrome is a pleiotropic disorder with 14 BBS genes identified. BBS1, BBS2, BBS4, BBS5, BBS7, BBS8, and BBS9 form a complex called the BBSome, which is believed to recruit Rab8(GTP) to the primary cilium and promote ciliogenesis. The second group, the chaperonin-like proteins BBS6, BBS10, and BBS12, have been defined as a vertebrate-specific branch of the type II chaperonin superfamily. These may play a role in the regulation of BBSome assembly.
  
  
  RESULTS
  Using sequence analysis, the role of BBS6, 10 and 12 was assessed in the patient population comprising 93 cases from 74 families. Systemic and ocular phenotypes were defined. In the study, chaperonin-like BBS gene mutations accounted for the disease in approximately 36.5% of BBS families. A total of 38 different non-polymorphic exonic sequence variants were identified in 40.5% of BBS families (41.9% cases), of which 26 were novel (68%). Six cases had mutations present in more than one chaperonin-like BBS gene. One case with four mutations in BBS10 had a phenotype of overall greater severity. The phenotypes observed were beyond the classic BBS phenotype as they overlapped with characteristics of MKKS (congenital heart defect, vaginal atresia, hydrometrocolpos, cryptorchidism), as well as Alström syndrome (diabetes, hearing loss, liver abnormalities, endocrine anomalies, cardiomyopathy).
  
  
  CONCLUSIONS
  While overlap between the MKKS and BBS phenotypes has previously been reported for cases with BBS6 mutations, we also observed MKKS phenotypes involving BBS10 and BBS12 and Alström-like phenotypes associated with mutations in BBS1, BBS2, BBS6, BBS7, BBS9, BBS10 and BBS12 for the first time.
authors.affiliation: Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada.
authors.forename: Gail
authors.initials: G
authors.lastname: Billingsley
authors.forename: Jenea
authors.initials: J
authors.lastname: Bin
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Fieggen
authors.forename: Jacque L
authors.initials: JL
authors.lastname: Duncan
authors.forename: Christina
authors.initials: C
authors.lastname: Gerth
authors.forename: Koji
authors.initials: K
authors.lastname: Ogata
authors.forename: Shoshana S
authors.initials: SS
authors.lastname: Wodak
authors.forename: Elias I
authors.initials: EI
authors.lastname: Traboulsi
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Fishman
authors.forename: Andrew
authors.initials: A
authors.lastname: Paterson
authors.forename: David
authors.initials: D
authors.lastname: Chitayat
authors.forename: Tanja
authors.initials: T
authors.lastname: Knueppel
authors.forename: José M
authors.initials: JM
authors.lastname: Millán
authors.forename: Grant A
authors.initials: GA
authors.lastname: Mitchell
authors.forename: Catherine
authors.initials: C
authors.lastname: Deveault
authors.forename: Elise
authors.initials: E
authors.lastname: Héon
mesh_terms: D000293:Adolescent; D000328:Adult; D056769:Alstrom Syndrome / Q000235:genetics; D020788:Bardet-Biedl Syndrome / Q000175:diagnosis / Q000235:genetics*; D018833:Chaperonins; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005190:Family; D005260:Female; D056385:Group II Chaperonins / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011487:Protein Conformation; D011506:Proteins; D012160:Retina / Q000473:pathology; D041623:Tomography, Optical Coherence
chemical_list: C512111:BBS10 protein, human; C517002:BBS12 protein, human; C414726:MKKS protein, human; D011506:Proteins; D018833:Chaperonins; D056385:Group II Chaperonins