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Original Investigation
March 2015

Association Between Missense Mutations in the BBS2 Gene and Nonsyndromic Retinitis Pigmentosa

Author Affiliations
  • 1Department of Ophthalmology, Hadassah–Hebrew University Medical Center, Jerusalem, Israel
  • 2Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, St James’s University Hospital, Leeds, England
  • 3Department of Genetics, Rappaport Faculty of Medicine and Research Institute, Technion–Israel Institute of Technology, Haifa, Israel
  • 4Center for Rare Jewish Genetic Disorders, Brooklyn, New York
JAMA Ophthalmol. 2015;133(3):312-318. doi:10.1001/jamaophthalmol.2014.5251

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.