title: Mutations in RPGR and RP2 account for 15% of males with simplex retinal degenerative disease.
abstract: OBJECTIVE
  To determine the proportion of male patients presenting simplex retinal degenerative disease (RD: retinitis pigmentosa [RP] or cone/cone-rod dystrophy [COD/CORD]) with mutations in the X-linked retinal degeneration genes RPGR and RP2.
  
  
  METHODS
  Simplex males were defined as patients with no known affected family members. Patients were excluded if they had a family history of parental consanguinity. Blood samples from a total of 214 simplex males with a diagnosis of retinal degeneration were collected for genetic analysis. The patients were screened for mutations in RPGR and RP2 by direct sequencing of PCR-amplified genomic DNA.
  
  
  RESULTS
  We identified pathogenic mutations in 32 of the 214 patients screened (15%). Of the 29 patients with a diagnosis of COD/CORD, four mutations were identified in the ORF15 mutational hotspot of the RPGR gene. Of the 185 RP patients, three patients had mutations in RP2 and 25 had RPGR mutations (including 12 in the ORF15 region).
  
  
  CONCLUSIONS
  This study represents mutation screening of RPGR and RP2 in the largest cohort, to date, of simplex males affected with RP or COD/CORD. Our results demonstrate a substantial contribution of RPGR mutations to retinal degenerations, and in particular, to simplex RP. Based on our findings, we suggest that RPGR should be considered as a first tier gene for screening isolated males with retinal degeneration.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan, Kellogg Eye Center, Ann Arbor, Michigan 48105, USA.
authors.forename: Kari
authors.initials: K
authors.lastname: Branham
authors.forename: Mohammad
authors.initials: M
authors.lastname: Othman
authors.forename: Matthew
authors.initials: M
authors.lastname: Brumm
authors.forename: Athanasios J
authors.initials: AJ
authors.lastname: Karoukis
authors.forename: Pelin
authors.initials: P
authors.lastname: Atmaca-Sonmez
authors.forename: Beverly M
authors.initials: BM
authors.lastname: Yashar
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Schwartz
authors.forename: Niamh B
authors.initials: NB
authors.lastname: Stover
authors.forename: Karmen
authors.initials: K
authors.lastname: Trzupek
authors.forename: Dianna
authors.initials: D
authors.lastname: Wheaton
authors.forename: Barbara
authors.initials: B
authors.lastname: Jennings
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Ciccarelli
authors.forename: K Thiran
authors.initials: KT
authors.lastname: Jayasundera
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lewis
authors.forename: David
authors.initials: D
authors.lastname: Birch
authors.forename: Jean
authors.initials: J
authors.lastname: Bennett
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sieving
authors.forename: Sten
authors.initials: S
authors.lastname: Andreasson
authors.forename: Jacque L
authors.initials: JL
authors.lastname: Duncan
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Fishman
authors.forename: Alessandro
authors.initials: A
authors.lastname: Iannaccone
authors.forename: Richard G
authors.initials: RG
authors.lastname: Weleber
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: John R
authors.initials: JR
authors.lastname: Heckenlively
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
mesh_terms: D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D019204:GTP-Binding Proteins; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D019105:Random Amplified Polymorphic DNA Technique; D012042:Registries; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D017678:Sex Distribution
chemical_list: D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C072178:RP2 protein, human; C099929:RPGR protein, human; D019204:GTP-Binding Proteins