title: BBS1 mutations in a wide spectrum of phenotypes ranging from nonsyndromic retinitis pigmentosa to Bardet-Biedl syndrome.
abstract: OBJECTIVE
  To investigate the involvement of the Bardet-Biedl syndrome (BBS) gene BBS1 p.M390R variant in nonsyndromic autosomal recessive retinitis pigmentosa (RP).
  
  
  METHODS
  Homozygosity mapping of a patient with isolated RP was followed by BBS1 sequence analysis. We performed restriction fragment length polymorphism analysis of the p.M390R allele in 2007 patients with isolated RP or autosomal recessive RP and in 1824 ethnically matched controls. Patients with 2 BBS1 variants underwent extensive clinical and ophthalmologic assessment.
  
  
  RESULTS
  In an RP proband who did not fulfill the clinical criteria for BBS, we identified a large homozygous region encompassing the BBS1 gene, which carried the p.M390R variant. In addition, this variant was detected homozygously in 10 RP patients and 1 control, compound heterozygously in 3 patients, and heterozygously in 5 patients and 6 controls. The 14 patients with 2 BBS1 variants showed the entire clinical spectrum, from nonsyndromic RP to full-blown BBS. In 8 of 14 patients, visual acuity was significantly reduced. In patients with electroretinographic responses, a rod-cone pattern of photoreceptor degeneration was observed.
  
  
  CONCLUSIONS
  Variants in BBS1 are significantly associated with nonsyndromic autosomal recessive RP and relatively mild forms of BBS. As exemplified in this study by the identification of a homozygous p.M390R variant in a control individual and in unaffected parents of BBS patients in other studies, cis - or trans -acting modifiers may influence the disease phenotype.
  
  
  CONCLUSIONS
  It is important to monitor patients with an early diagnosis of mild BBS phenotypes for possible life-threatening conditions.
authors.affiliation: Departments of Human Genetics, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, the Netherlands.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Estrada-Cuzcano
authors.forename: Robert K
authors.initials: RK
authors.lastname: Koenekoop
authors.forename: Audrey
authors.initials: A
authors.lastname: Senechal
authors.forename: Elfride B W
authors.initials: EB
authors.lastname: De Baere
authors.forename: Thomy
authors.initials: T
authors.lastname: de Ravel
authors.forename: Sandro
authors.initials: S
authors.lastname: Banfi
authors.forename: Susanne
authors.initials: S
authors.lastname: Kohl
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.forename: Dror
authors.initials: D
authors.lastname: Sharon
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hamel
authors.forename: Bart P
authors.initials: BP
authors.lastname: Leroy
authors.forename: Carmela
authors.initials: C
authors.lastname: Ziviello
authors.forename: Irma
authors.initials: I
authors.lastname: Lopez
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bazinet
authors.forename: Bernd
authors.initials: B
authors.lastname: Wissinger
authors.forename: Ieva
authors.initials: I
authors.lastname: Sliesoraityte
authors.forename: Almudena
authors.initials: A
authors.lastname: Avila-Fernandez
authors.forename: Karin W
authors.initials: KW
authors.lastname: Littink
authors.forename: Enzo M
authors.initials: EM
authors.lastname: Vingolo
authors.forename: Sabrina
authors.initials: S
authors.lastname: Signorini
authors.forename: Eyal
authors.initials: E
authors.lastname: Banin
authors.forename: Liliana
authors.initials: L
authors.lastname: Mizrahi-Meissonnier
authors.forename: Eberhard
authors.initials: E
authors.lastname: Zrenner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kellner
authors.forename: Rob W J
authors.initials: RW
authors.lastname: Collin
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.forename: B Jeroen
authors.initials: BJ
authors.lastname: Klevering
mesh_terms: D000328:Adult; D000483:Alleles; D020788:Bardet-Biedl Syndrome / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D002170:Canada / Q000453:epidemiology; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005006:Ethnicity; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008297:Male; D033401:Microscopy, Acoustic; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020125:Mutation, Missense; D009887:Ophthalmoscopy; D010375:Pedigree; D010641:Phenotype; D015995:Prevalence; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*
chemical_list: C464790:Bbs1 protein, human; D008869:Microtubule-Associated Proteins; D004247:DNA