Association between missense mutations in the BBS2 gene and nonsyndromic retinitis pigmentosa

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.