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Alejandro Estrada Cuzcano, Robert K. Koenekoop, European Retinal Disease Consortium study group, Anneke I. Den Hollander, Jeroen B. Klevering, Frans P. Cremers; Mutations In BBS1 Cause Mild Bardet-Biedl Syndrome And Nonsyndromic Retinal Dystrophy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2375.
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Evaluation of the involvement of the BBS1 gene in patients with autosomal recessive retinal dystrophies (arRD).
Homozygosity mapping in 330 arRD patients was performed using 250K SNP microarrays. Restriction fragment length polymorphism (RFLP) analysis was performed to detect the BBS1 M390R mutation in European and Canadian arRD patients and anonymous controls, followed by sequence analysis of all BBS1 exons in patients with one M390R allele
One arRD patient showed a 19-Mb homozygous region encompassing BBS1, which is mutated in patients with Bardet-Biedl syndrome (BBS). This patient carried the most frequent BBS1 variant, M390R, homozygously. Apart from a severe retinal degeneration and cataract, this patient was obese but did not show any other typical BBS features. This prompted us to perform RFLP analysis of this variant in 2304 unrelated arRD patients and 1824 controls from Europe and Canada, which revealed 12 mild BBS/arRD patients homozygous for M390R, two patients with mild BBS/arRD that carried this variant compound heterozygously, and 5 arRD patients carrying one heterozygous M390R mutation. RFLP analysis in controls revealed one homozygous and six heterozygous M390R carriers
BBS1 variants previously were found in patients with classical BBS, with or without modifier alleles in other ciliary genes, and in unaffected individuals. We identified two BBS1 variants in individuals with a wide clinical spectrum ranging from classical BBS to nonsyndromic arRD, as well as in one putative healthy individual. Although the BBS1 mutation M390R was found homozygously in one control individual, suggesting that it is not pathogenic on its own, it was found significantly more frequent in patients (p = 0.003). Additional studies are ongoing to explain the variable clinical pictures associated with two BBS1 alleles
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