title: Association between missense mutations in the BBS2 gene and nonsyndromic retinitis pigmentosa.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Patients and family members were recruited for the study and underwent clinical evaluation and genetic analyses.
  
  
  METHODS
  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
  Our study shows that BBS2 mutations can cause nonsyndromic retinitis pigmentosa and highlights yet another candidate for this genetically heterogeneous condition.
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Elia
authors.initials: E
authors.lastname: Shevach
authors.affiliation: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, St James's University Hospital, Leeds, England.
authors.forename: Manir
authors.initials: M
authors.lastname: Ali
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Liliana
authors.initials: L
authors.lastname: Mizrahi-Meissonnier
authors.affiliation: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, St James's University Hospital, Leeds, England.
authors.forename: Martin
authors.initials: M
authors.lastname: McKibbin
authors.affiliation: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, St James's University Hospital, Leeds, England.
authors.forename: Mohammed
authors.initials: M
authors.lastname: El-Asrag
authors.affiliation: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, St James's University Hospital, Leeds, England.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Watson
authors.affiliation: Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, St James's University Hospital, Leeds, England.
authors.forename: Chris F
authors.initials: CF
authors.lastname: Inglehearn
authors.affiliation: Department of Genetics, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Ben-Yosef
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Blumenfeld
authors.affiliation: Center for Rare Jewish Genetic Disorders, Brooklyn, New York.
authors.forename: Chaim
authors.initials: C
authors.lastname: Jalas
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Banin
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Sharon
mesh_terms: D000328:Adult; D000368:Aged; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004585:Electrooculography; D004596:Electroretinography; D059472:Exome / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D060005:Genotyping Techniques; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: C473309:Bbs2 protein, human; D011506:Proteins