title: Retinal Diseases Caused by Mutations in Genes Not Specifically Associated with the Clinical Diagnosis.
abstract: OBJECTIVE
  When seeking a confirmed molecular diagnosis in the research setting, patients with one descriptive diagnosis of retinal disease could carry pathogenic variants in genes not specifically associated with that description. However, this event has not been evaluated systematically in clinical diagnostic laboratories that validate fully all target genes to minimize false negatives/positives.
  
  
  METHODS
  We performed targeted next-generation sequencing analysis on 207 ocular disease-related genes for 42 patients whose DNA had been tested negative for disease-specific panels of genes known to be associated with retinitis pigmentosa, Leber congenital amaurosis, or exudative vitreoretinopathy.
  
  
  RESULTS
  Pathogenic variants, including single nucleotide variations and copy number variations, were identified in 9 patients, including 6 with variants in syndromic retinal disease genes and 3 whose molecular diagnosis could not be distinguished easily from their submitted clinical diagnosis, accounting for 21% (9/42) of the unsolved cases.
  
  
  CONCLUSIONS
  Our study underscores the clinical and genetic heterogeneity of retinal disorders and provides valuable reference to estimate the fraction of clinical samples whose retinal disorders could be explained by genes not specifically associated with the corresponding clinical diagnosis. Our data suggest that sequencing a larger set of retinal disorder related genes can increase the molecular diagnostic yield, especially for clinically hard-to-distinguish cases.
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Xia
authors: http://orcid.org/0000-0002-7750-1167
authors: X
authors: Wang
authors: Baylor Genetics, Houston, Texas, United States of America.
authors: Yanming
authors: Y
authors: Feng
authors: Baylor Genetics, Houston, Texas, United States of America.
authors: Jianli
authors: J
authors: Li
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Wei
authors: W
authors: Zhang
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Jing
authors: J
authors: Wang
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.|Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States of America.
authors: Richard A
authors: RA
authors: Lewis
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.|Baylor Genetics, Houston, Texas, United States of America.
authors: Lee-Jun
authors: LJ
authors: Wong
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D009154:Mutation; D012164:Retinal Diseases / Q000175:diagnosis* / Q000235:genetics*