title: Genotype-phenotype correlation and mutation spectrum in a large cohort of patients with inherited retinal dystrophy revealed by next-generation sequencing.
abstract: OBJECTIVE
  Inherited retinal dystrophy (IRD) is a leading cause of blindness worldwide. Because of extreme genetic heterogeneity, the etiology and genotypic spectrum of IRD have not been clearly defined, and there is limited information on genotype-phenotype correlations. The purpose of this study was to elucidate the mutational spectrum and genotype-phenotype correlations of IRD.
  
  
  METHODS
  We developed a targeted panel of 164 known retinal disease genes, 88 candidate genes, and 32 retina-abundant microRNAs, used for exome sequencing. A total of 179 Chinese families with IRD were recruited.
  
  
  RESULTS
  In 99 unrelated patients, a total of 124 mutations in known retinal disease genes were identified, including 79 novel mutations (detection rate, 55.3%). Moreover, novel genotype-phenotype correlations were discovered, and phenotypic trends noted. Three cases are reported, including the identification of AHI1 as a novel candidate gene for nonsyndromic retinitis pigmentosa.
  
  
  CONCLUSIONS
  This study revealed novel genotype-phenotype correlations, including a novel candidate gene, and identified 124 genetic defects within a cohort with IRD . The identification of novel genotype-phenotype correlations and the spectrum of mutations greatly enhance the current knowledge of IRD phenotypic and genotypic heterogeneity, which will assist both clinical diagnoses and personalized treatments of IRD patients.
authors.affiliation: The Eye Hospital of Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health, Wenzhou, China.
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Huang
authors.affiliation: The Eye Hospital of Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health, Wenzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.affiliation: The Eye Hospital of Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health, Wenzhou, China.
authors.forename: Kun-Chao
authors.initials: KC
authors.lastname: Wu
authors.affiliation: The Eye Hospital of Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health, Wenzhou, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wu
authors.affiliation: The Eye Hospital of Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health, Wenzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Chi-Pui
authors.initials: CP
authors.lastname: Pang
authors.affiliation: The Eye Hospital of Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health, Wenzhou, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Lu
authors.affiliation: The Eye Hospital of Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health, Wenzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.affiliation: The Eye Hospital of Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health, Wenzhou, China.
authors.forename: Zi-Bing
authors.identifier: 000000030515698X
authors.initials: ZB
authors.lastname: Jin
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D059472:Exome / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D058499:Retinal Dystrophies / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology