IMPORTANCE: A large number of genes can cause inherited retinal degenerations when mutated. It is important to identify the cause of disease for a better disease prognosis and a possible gene-specific therapeutic intervention. OBJECTIVE: To identify the cause of disease in families with nonsyndromic retinitis pigmentosa. DESIGN, SETTING, AND PARTICIPANTS: Patients and family members were recruited for the study and underwent clinical evaluation and genetic analyses. MAIN OUTCOMES AND MEASURES: Identification of sequence variants in genes using next-generation sequencing. RESULTS: We performed exome sequencing for 4 families, which was followed by Sanger sequencing of the identified mutations in 120 ethnicity-matched patients. In total, we identified 4 BBS2 missense mutations that cause nonsyndromic retinitis pigmentosa. Three siblings of Moroccan Jewish ancestry were compound heterozygotes for p.A33D and p.P134R, and 6 patients belonging to 4 families of Ashkenazi Jewish ancestry were homozygous for either p.D104A or p.R632P, or compound heterozygous for these 2 mutations. The mutations cosegregated with retinitis pigmentosa in the studied families, and the affected amino acid residues are evolutionarily conserved. CONCLUSIONS AND RELEVANCE: Our study shows that BBS2 mutations can cause nonsyndromic retinitis pigmentosa and highlights yet another candidate for this genetically heterogeneous condition.
IMPORTANCE: A large number of genes can cause inherited retinal degenerations when mutated. It is important to identify the cause of disease for a better disease prognosis and a possible gene-specific therapeutic intervention. OBJECTIVE: To identify the cause of disease in families with nonsyndromic retinitis pigmentosa. DESIGN, SETTING, AND PARTICIPANTS: Patients and family members were recruited for the study and underwent clinical evaluation and genetic analyses. MAIN OUTCOMES AND MEASURES: Identification of sequence variants in genes using next-generation sequencing. RESULTS: We performed exome sequencing for 4 families, which was followed by Sanger sequencing of the identified mutations in 120 ethnicity-matched patients. In total, we identified 4 BBS2 missense mutations that cause nonsyndromic retinitis pigmentosa. Three siblings of Moroccan Jewish ancestry were compound heterozygotes for p.A33D and p.P134R, and 6 patients belonging to 4 families of Ashkenazi Jewish ancestry were homozygous for either p.D104A or p.R632P, or compound heterozygous for these 2 mutations. The mutations cosegregated with retinitis pigmentosa in the studied families, and the affected amino acid residues are evolutionarily conserved. CONCLUSIONS AND RELEVANCE: Our study shows that BBS2 mutations can cause nonsyndromic retinitis pigmentosa and highlights yet another candidate for this genetically heterogeneous condition.
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: Laurence H M Pierrache; Adva Kimchi; Rinki Ratnapriya; Lisa Roberts; Galuh D N Astuti; Alexey Obolensky; Avigail Beryozkin; Martha J H Tjon-Fo-Sang; Jose Schuil; Caroline C W Klaver; Ernie M H F Bongers; Lonneke Haer-Wigman; Nicoline Schalij; Martijn H Breuning; Gratia M Fischer; Eyal Banin; Raj S Ramesar; Anand Swaroop; L Ingeborgh van den Born; Dror Sharon; Frans P M Cremers Journal: Ophthalmology Date: 2017-04-13 Impact factor: 12.079
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
Authors: Nicole Weisschuh; Anja K Mayer; Tim M Strom; Susanne Kohl; Nicola Glöckle; Max Schubach; Sten Andreasson; Antje Bernd; David G Birch; Christian P Hamel; John R Heckenlively; Samuel G Jacobson; Christina Kamme; Ulrich Kellner; Erdmute Kunstmann; Pietro Maffei; Charlotte M Reiff; Klaus Rohrschneider; Thomas Rosenberg; Günther Rudolph; Rita Vámos; Balázs Varsányi; Richard G Weleber; Bernd Wissinger Journal: PLoS One Date: 2016-01-14 Impact factor: 3.240