title: Phenotypic conservation in patients with X-linked retinitis pigmentosa caused by RPGR mutations.
abstract: OBJECTIVE
  For patients with X-linked retinitis pigmentosa and clinicians alike, phenotypic variability can be challenging because it complicates counseling regarding patients' likely visual prognosis.
  
  
  OBJECTIVE
  To evaluate the clinical findings from patients with X-linked retinitis pigmentosa with 13 distinct RPGR mutations and assess for phenotypic concordance or variability.
  
  
  METHODS
  Retrospective medical record review of data collected from 1985 to 2011.
  
  
  METHODS
  Kellogg Eye Center, University of Michigan.
  
  
  METHODS
  A total of 42 patients with X-linked retinitis pigmentosa with mutations in RPGR. Age at first visit ranged from 4 to 53 years, with follow-up ranging from 1 to 11 visits (median follow-up time, 5.5 years; range, 1.4-32.7 years, for 23 patients with >1 visit).
  
  
  METHODS
  Clinical data assessed for concordance included visual acuity (VA), Goldmann visual fields (GVFs), and full-field electroretinography (ERG). Electroretinography phenotype (cone-rod vs rod-cone dysfunction) was defined by the extent of photopic vs scotopic abnormality. Qualitative GVF phenotype was determined by the GVF pattern, where central or peripheral loss suggested cone or rod dysfunction, respectively. Goldmann visual fields were also quantified and compared among patients.
  
  
  RESULTS
  Each mutation was detected in 2 or more related or unrelated patients. Five mutations in 11 patients displayed strong concordance of VA, while 4 mutations in 16 patients revealed moderate concordance of VA. A definitive cone-rod or rod-cone ERG pattern consistent among patients was found in 6 of 13 mutations (46.2%); the remaining mutations were characterized by patients demonstrating both phenotypes or who had limited data or nonrecordable ERG values. Concordant GVF phenotypes (7 rod-cone pattern vs 4 cone-rod pattern) were seen in 11 of 13 mutations (84.6%). All 6 mutations displaying a constant ERG pattern within the mutation group revealed a GVF phenotype consistent with the ERG findings.
  
  
  CONCLUSIONS
  While VA and ERG phenotypes are concordant in only some patients carrying identical mutations, assessment of GVF phenotypes revealed stronger phenotypic conservation. Phenotypic concordance is important for establishing proper counseling of patients diagnosed as having X-linked retinitis pigmentosa, as well as for establishing accurate patient selection and efficacy monitoring in therapeutic trials.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, MI 48105, USA.
authors.forename: Sarwar
authors.initials: S
authors.lastname: Zahid
authors.forename: Naheed
authors.initials: N
authors.lastname: Khan
authors.forename: Kari
authors.initials: K
authors.lastname: Branham
authors.forename: Mohammad
authors.initials: M
authors.lastname: Othman
authors.forename: Athanasios J
authors.initials: AJ
authors.lastname: Karoukis
authors.forename: Nisha
authors.initials: N
authors.lastname: Sharma
authors.forename: Ashley
authors.initials: A
authors.lastname: Moncrief
authors.forename: Mahdi N
authors.initials: MN
authors.lastname: Mahmood
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sieving
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
authors.forename: John R
authors.initials: JR
authors.lastname: Heckenlively
authors.forename: Thiran
authors.initials: T
authors.lastname: Jayasundera
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D012189:Retrospective Studies; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult
chemical_list: D005136:Eye Proteins; C099929:RPGR protein, human