Title: BBS1 Mutations in a Wide Spectrum of Phenotypes Ranging From Nonsyndromic Retinitis Pigmentosa to Bardet-Biedl Syndrome
Authors: Estrada-Cuzcano, Alejandro ×
Koenekoop, Robert K
Senechal, Audrey
De Baere, Elfride B W
de Ravel de l'Argentière, Thomy
Banfi, Sandro
Kohl, Susanne
Ayuso, Carmen
Sharon, Dror
Hoyng, Carel B
Hamel, Christian P
Leroy, Bart P
Ziviello, Carmela
Lopez, Irma
Bazinet, Alexandre
Wissinger, Bernd
Sliesoraityte, Ieva
Avila-Fernandez, Almudena
Littink, Karin W
Vingolo, Enzo M
Signorini, Sabrina
Banin, Eyal
Mizrahi-Meissonnier, Liliana
Zrenner, Eberhard
Kellner, Ulrich
Collin, Rob W J
den Hollander, Anneke I
Cremers, Frans P M
Klevering, B Jeroen #
Issue Date: Nov-2012
Publisher: American Medical Association
Series Title: Archives of Ophthalmology vol:130 issue:11 pages:1425-1432
Article number: 10.1001/archophthalmol.2012.2434
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. CLINICAL RELEVANCE It is important to monitor patients with an early diagnosis of mild BBS phenotypes for possible life-threatening conditions.
ISSN: 0003-9950
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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