title: Detecting genetic variations in hereditary retinal dystrophies with next-generation sequencing technology.
abstract: OBJECTIVE
  To identify pathogenic mutations responsible for retinal dystrophies (RDs) in three unrelated Chinese families.
  
  
  METHODS
  Three probands from unrelated families with RDs were recruited. Genomic DNA prepared from leukocytes was analyzed using gene chip-based next-generation sequencing (NGS) to capture and sequence all of the exons of 100 known RD-associated genes. Candidate variants were validated with PCR and Sanger sequencing in the respective families. Thorough ophthalmic examinations including best-corrected visual acuity, funduscopic examination, and full-field electroretinograms were performed in the affected individuals.
  
  
  RESULTS
  We successfully identified causative mutations in patients from the Chinese families with RDS: the known mutation IMPDH1 c.942_944delGAA in a family with retinitis pigmentosa, the novel mutation ABCA4 c.1924T>A in a family with Stargardt disease, and the novel mutation NMNAT1 c.272A>G and known mutation NMNAT1 c.196C>T in a family with Leber congenital amaurosis. All variations segregated with the disease phenotypes in the respective families and were absent from ethnically matched control chromosomes. Prediction analysis demonstrated the two novel missense mutations might be damaging.
  
  
  CONCLUSIONS
  The results strongly suggested these mutations were responsible for different RD phenotypes in the Chinese families. NGS technology provides an accurate and economic method for identifying causative genes for RDs.
authors.affiliation: Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing, China ; Department of Ophthalmology, Chinese PLA General Hospital, Beijing, China ; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing, China ; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, China.
authors.forename: Ling Hui
authors.initials: LH
authors.lastname: Qu
authors.affiliation: Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing, China ; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, China.
authors.forename: Xiao Hong
authors.initials: XH
authors.lastname: Meng
authors.affiliation: Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing, China ; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, China.
authors.forename: Hai Wei
authors.initials: HW
authors.lastname: Xu
authors.affiliation: Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing, China ; Department of Ophthalmology, Chinese PLA General Hospital, Beijing, China ; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, China.
authors.forename: Zheng Qin
authors.initials: ZQ
authors.lastname: Yin
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D004596:Electroretinography; D005190:Family; D005260:Female; D005654:Fundus Oculi; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D058499:Retinal Dystrophies / Q000235:genetics* / Q000503:physiopathology