title: Genotype-phenotype correlations in Bardet-Biedl syndrome.
abstract: OBJECTIVE
  To determine whether mutations in different Bardet-Biedl syndrome (BBS) genes result in different ocular phenotypes.
  
  
  METHODS
  Thirty-seven patients from 31 families were enrolled who met the clinical criteria for BBS and for whom a BBS mutation had been identified. Seventeen patients harbored mutations in BBS1, 10 in BBS10, and 10 in other genes (BBS2, BBS3, BBS5, BBS7, and BBS12). All the patients underwent ocular examination; 36 patients had computerized full-field electroretinograms (ERGs).
  
  
  RESULTS
  Visual acuity was significantly better in BBS1 patients than in patients with other BBS mutations (P=.01), and a larger proportion of BBS1 patients had good (≥20/50) visual acuity (P=.01). The ERG amplitudes were significantly higher in BBS1 patients than in patients with other BBS mutations in response to 0.5-Hz and 30-Hz flashes (P<.001 for both). All the BBS1 patients harbored at least 1 missense mutation compared with only 45% of patients with mutations in other BBS genes (P<.001); the rest harbored only null alleles. However, multivariate analysis demonstrated that visual acuity or ERG amplitude did not depend on the type of mutation present (missense or null) when controlling for BBS gene. Prevalences of bone spicule pigmentation and cataract were comparable in BBS subtypes.
  
  
  CONCLUSIONS
  Patients with BBS1 mutations had a milder phenotype than did patients with mutations in other BBS genes. Clinically, this manifested as significantly better visual acuity and larger ERG amplitudes.
  
  
  CONCLUSIONS
  These phenotypic differences can help guide genetic testing and genetic counseling for patients with this syndrome.
authors.affiliation: Berman-Gund Laboratory for the Study of Retinal Degenerations, Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Daniels
authors.forename: Michael A
authors.initials: MA
authors.lastname: Sandberg
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
authors.forename: Carol
authors.initials: C
authors.lastname: Weigel-DiFranco
authors.forename: J
authors.initials: J
authors.lastname: Fielding Hejtmancic
authors.forename: Eliot L
authors.initials: EL
authors.lastname: Berson
mesh_terms: D000293:Adolescent; D000328:Adult; D020788:Bardet-Biedl Syndrome / Q000235:genetics* / Q000503:physiopathology; D018833:Chaperonins; D002648:Child; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005260:Female; D056726:Genetic Association Studies; D056385:Group II Chaperonins / Q000235:genetics; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D012160:Retina / Q000503:physiopathology*; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult
chemical_list: C512111:BBS10 protein, human; C464790:Bbs1 protein, human; D008869:Microtubule-Associated Proteins; D018833:Chaperonins; D056385:Group II Chaperonins