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.
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.
Authors: Frans P M Cremers; Johan T den Dunnen; Muhammad Ajmal; Alamdar Hussain; Markus N Preising; Stephen P Daiger; Raheel Qamar Journal: Hum Mutat Date: 2014-01 Impact factor: 4.878
Authors: Ruben Jauregui; Amanda L Thomas; Benjamin Liechty; Gabriel Velez; Vinit B Mahajan; Lorraine Clark; Stephen H Tsang Journal: Am J Med Genet A Date: 2018-12-18 Impact factor: 2.802
Authors: Feng Wang; Hui Wang; Han-Fang Tuan; Duy H Nguyen; Vincent Sun; Vafa Keser; Sara J Bowne; Lori S Sullivan; Hongrong Luo; Ling Zhao; Xia Wang; Jacques E Zaneveld; Jason S Salvo; Sorath Siddiqui; Louise Mao; Dianna K Wheaton; David G Birch; Kari E Branham; John R Heckenlively; Cindy Wen; Ken Flagg; Henry Ferreyra; Jacqueline Pei; Ayesha Khan; Huanan Ren; Keqing Wang; Irma Lopez; Raheel Qamar; Juan C Zenteno; Raul Ayala-Ramirez; Beatriz Buentello-Volante; Qing Fu; David A Simpson; Yumei Li; Ruifang Sui; Giuliana Silvestri; Stephen P Daiger; Robert K Koenekoop; Kang Zhang; Rui Chen Journal: Hum Genet Date: 2013-10-24 Impact factor: 4.132
Authors: Cristy A Ku; Sarah Hull; Gavin Arno; Ajoy Vincent; Keren Carss; Robert Kayton; Douglas Weeks; Glenn W Anderson; Ryan Geraets; Camille Parker; David A Pearce; Michel Michaelides; Robert E MacLaren; Anthony G Robson; Graham E Holder; Elise Heon; F Lucy Raymond; Anthony T Moore; Andrew R Webster; Mark E Pennesi Journal: JAMA Ophthalmol Date: 2017-07-01 Impact factor: 7.389
Authors: Anna M Siemiatkowska; Rob W J Collin; Anneke I den Hollander; Frans P M Cremers Journal: Cold Spring Harb Perspect Med Date: 2014-06-17 Impact factor: 6.915
Authors: Kinga M Bujakowska; Qi Zhang; Anna M Siemiatkowska; Qin Liu; Emily Place; Marni J Falk; Mark Consugar; Marie-Elise Lancelot; Aline Antonio; Christine Lonjou; Wassila Carpentier; Saddek Mohand-Saïd; Anneke I den Hollander; Frans P M Cremers; Bart P Leroy; Xiaowu Gai; José-Alain Sahel; L Ingeborgh van den Born; Rob W J Collin; Christina Zeitz; Isabelle Audo; Eric A Pierce Journal: Hum Mol Genet Date: 2014-08-28 Impact factor: 6.150
Authors: Yangfan P Liu; Daniëlle G M Bosch; Anna M Siemiatkowska; Nanna Dahl Rendtorff; F Nienke Boonstra; Claes Möller; Lisbeth Tranebjærg; Nicholas Katsanis; Frans P M Cremers Journal: Ophthalmic Genet Date: 2016-03-30 Impact factor: 1.803
Authors: Katie Weihbrecht; Wesley A Goar; Thomas Pak; Janelle E Garrison; Adam P DeLuca; Edwin M Stone; Todd E Scheetz; Val C Sheffield Journal: Med Res Arch Date: 2017-09-18