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

  • JAMA Ophthalmol. 2015 Mar;133(3):312-8. doi: 10.1001/jamaophthalmol.2014.5251.
Elia Shevach  1 ,  Manir Ali  2 ,  Liliana Mizrahi-Meissonnier  1 ,  Martin McKibbin  2 ,  Mohammed El-Asrag  2 ,  Christopher M Watson  2 ,  Chris F Inglehearn  2 ,  Tamar Ben-Yosef  3 ,  Anat Blumenfeld  1 ,  Chaim Jalas  4 ,  Eyal Banin  1 ,  Dror Sharon  1
Affiliations
  • 1. Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • 2. Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, St James's University Hospital, Leeds, England.
  • 3. Department of Genetics, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
  • 4. Center for Rare Jewish Genetic Disorders, Brooklyn, New York.
PMID: 25541840 DOI: 10.1001/jamaophthalmol.2014.5251
Abstract

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.