title: De Novo Occurrence of a Variant in ARL3 and Apparent Autosomal Dominant Transmission of Retinitis Pigmentosa.
abstract: BACKGROUND
  Retinitis pigmentosa is a phenotype with diverse genetic causes. Due to this genetic heterogeneity, genome-wide identification and analysis of protein-altering DNA variants by exome sequencing is a powerful tool for novel variant and disease gene discovery. In this study, exome sequencing analysis was used to search for potentially causal DNA variants in a two-generation pedigree with apparent dominant retinitis pigmentosa.
  
  
  METHODS
  Variant identification and analysis of three affected members (mother and two affected offspring) was performed via exome sequencing. Parental samples of the index case were used to establish inheritance. Follow-up testing of 94 additional retinitis pigmentosa pedigrees was performed via retrospective analysis or Sanger sequencing.
  
  
  CONCLUSIONS
  A total of 136 high quality coding variants in 123 genes were identified which are consistent with autosomal dominant disease. Of these, one of the strongest genetic and functional candidates is a c.269A>G (p.Tyr90Cys) variant in ARL3. Follow-up testing established that this variant occurred de novo in the index case. No additional putative causal variants in ARL3 were identified in the follow-up cohort, suggesting that if ARL3 variants can cause adRP it is an extremely rare phenomenon.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Samuel P
authors.initials: SP
authors.lastname: Strom
authors.affiliation: Personalis Inc., Menlo Park, California, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Clark
authors.affiliation: Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Ariadna
authors.initials: A
authors.lastname: Martinez
authors.affiliation: Personalis Inc., Menlo Park, California, United States of America.
authors.forename: Sarah
authors.initials: S
authors.lastname: Garcia
authors.affiliation: Research Institute of Ophthalmology, Cairo, Egypt.
authors.forename: Amira A
authors.initials: AA
authors.lastname: Abelazeem
authors.affiliation: Jules Stein Eye Institute and Department of Ophthalmology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Matynia
authors.affiliation: Jules Stein Eye Institute and Department of Ophthalmology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Sachin
authors.initials: S
authors.lastname: Parikh
authors.affiliation: Human Genetics Center, University of Texas Health Science Center, Houston, Texas, United States of America.
authors.forename: Lori S
authors.initials: LS
authors.lastname: Sullivan
authors.affiliation: Human Genetics Center, University of Texas Health Science Center, Houston, Texas, United States of America.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Bowne
authors.affiliation: Human Genetics Center, University of Texas Health Science Center, Houston, Texas, United States of America.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Daiger
authors.affiliation: Jules Stein Eye Institute and Department of Ophthalmology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Gorin
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics*; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D012174:Retinitis Pigmentosa / Q000235:genetics*
chemical_list: D020727:ADP-Ribosylation Factors; C490247:ARL3 protein, human