BBS1 mutations in a wide spectrum of phenotypes ranging from nonsyndromic retinitis pigmentosa to bardet-biedl syndrome

Alejandro Estrada-Cuzcano, Robert K. Koenekoop, Audrey Senechal, Elfride B W De Baere, Thomy De Ravel, Sandro Banfi, Susanne Kohl, Carmen Ayuso, Dror Sharon, Carel B. Hoyng, Christian P. Hamel, Bart P. Leroy, Carmela Ziviello, Irma Lopez, Alexandre Bazinet, Bernd Wissinger, Ieva Sliesoraityte, Almudena Avila-Fernandez, Karin W. Littink, Enzo M. VingoloSabrina Signorini, Eyal Banin, Liliana Mizrahi-Meissonnier, Eberhard Zrenner, Ulrich Kellner, Rob W J Collin, Anneke I. Den Hollander, Frans P M Cremers, B. Jeroen Klevering

Research output: Contribution to journalArticlepeer-review


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. Clinical Relevance: It is important to monitor patients with an early diagnosis of mild BBS phenotypes for possible life-threatening conditions.

Original languageEnglish
Pages (from-to)1425-1432
Number of pages8
JournalArchives of Ophthalmology
Issue number11
Publication statusPublished - Nov 2012

ASJC Scopus subject areas

  • Ophthalmology


Dive into the research topics of 'BBS1 mutations in a wide spectrum of phenotypes ranging from nonsyndromic retinitis pigmentosa to bardet-biedl syndrome'. Together they form a unique fingerprint.

Cite this