title: Autosomal Dominant Retinal Dystrophy With Electronegative Waveform Associated With a Novel RAX2 Mutation.
abstract: OBJECTIVE
  The patients evaluated in this study, to our knowledge, represent the first complete clinical description of a family with an autosomal dominant inheritance pattern of retinal dystrophy associated with a novel mutation in RAX2.
  
  
  OBJECTIVE
  To clinically evaluate 4 patients and 5 unaffected family members, characterize the disease phenotype over time, and identify the associated genetic mutation.
  
  
  METHODS
  A prospective, longitudinal, observational, case-series analysis of 9 members of an affected family at the Casey Eye Institute, Oregon Health and Science University, Portland. The dates of the study were from July 31, 1992, to August 11, 2014.
  
  
  METHODS
  Clinical evaluations included eye examination, color fundus photography, autofluorescence imaging, spectral-domain optical coherence tomography, kinetic visual field testing, and electroretinography. Genetic mutation screening was performed with next-generation sequencing, and identified mutations were confirmed with Sanger sequencing.
  
  
  METHODS
  Clinical diagnosis and longitudinal characterization of retinal dystrophy and identification of genetic mutation.
  
  
  RESULTS
  Six members of the family were identified as having retinal dystrophy (4 were examined, and 3 were genetically tested). Five unaffected family members were clinically evaluated (2 were genetically tested). The age at onset of retinal dystrophy was variable. All affected individuals presented with declining visual acuity, central scotomas, waxy disc pallor, attenuated vasculature, small yellow macular deposits and/or macular pigment mottling, and abnormal electroretinograms demonstrating mixed cone and rod dysfunction and a scotopic electronegative response to bright flashes. There were no other causes of an electronegative electroretinogram identified in any of the affected patients. Genetic testing revealed, to our knowledge, a novel frameshift heterozygous mutation in RAX2 in the patients with retinal dystrophy.
  
  
  CONCLUSIONS
  A frameshift heterozygous mutation in RAX2 inherited in an autosomal dominant fashion was associated with mixed cone and rod dysfunction. Among the patients, there was variability in the age at onset and in the specific pattern of photoreceptor dysfunction, but the clinical course was nevertheless slowly progressive. Screening for RAX2 mutation could provide prognostic value for patients and families with scotopic electronegative responses to bright flashes.
authors: Casey Eye Institute, Oregon Health and Science University, Portland.
authors: Paul
authors: P
authors: Yang
authors: Casey Eye Institute, Oregon Health and Science University, Portland.
authors: Pei-Wen
authors: PW
authors: Chiang
authors: Casey Eye Institute, Oregon Health and Science University, Portland.
authors: Richard G
authors: RG
authors: Weleber
authors: Casey Eye Institute, Oregon Health and Science University, Portland.
authors: Mark E
authors: ME
authors: Pennesi
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D016368:Frameshift Mutation; D059014:High-Throughput Nucleotide Sequencing; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D041623:Tomography, Optical Coherence; D014157:Transcription Factors / Q000235:genetics*; D058609:Visual Field Tests; D014794:Visual Fields; D055815:Young Adult
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; C486393:RAX protein, human; D014157:Transcription Factors