title: Comprehensive Molecular Diagnosis of a Large Chinese Leber Congenital Amaurosis Cohort.
abstract: OBJECTIVE
  Leber congenital amaurosis (LCA) is an inherited retinal disease that causes early-onset severe visual impairment. To evaluate the mutation spectrum in the Chinese population, we performed a mutation screen in 145 Chinese LCA families.
  
  
  METHODS
  First, we performed direct Sanger sequencing of 7 LCA disease genes in 81 LCA families. Next, we developed a capture panel that enriches the entire coding exons and splicing sites of 163 known retinal disease genes and other candidate retinal disease genes. The capture panel allowed us to quickly identify disease-causing mutations in a large number of genes at a relatively low cost. Thus, this method was applied to the 53 LCA families that were unsolved by direct Sanger sequencing of 7 LCA disease genes and an additional 64 LCA families. Systematic next-generation sequencing (NGS) data analysis, Sanger sequencing validation, and segregation analysis were used to identify pathogenic mutations.
  
  
  RESULTS
  Homozygous or compound heterozygous mutations were identified in 107 families, heterozygous autosomal dominant mutations were identified in 3 families and an X-linked mutation was found in 1 family, for a combined solving rate of 76.6%. In total, 136 novel pathogenic mutations were found in this study. In combination with two previous studies carried out in Chinese LCA patients, we concluded that the mutation spectrum in the Chinese population is distinct compared to that in the European population. After revisiting, we also refined the clinical diagnosis of 10 families based on their molecular diagnosis.
  
  
  CONCLUSIONS
  Our results highlight the importance of a molecular diagnosis as an integral part of the clinical diagnostic process.
authors.affiliation: Institute of Developmental and Regenerative Biology Hangzhou Normal University, Jianggan, Hangzhou, Zhejiang, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States 3Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Dongcheng, Beijing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zou
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States.
authors.forename: Shan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Dongcheng, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States.
authors.forename: Zachry Tore
authors.initials: ZT
authors.lastname: Soens
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States 3Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States.
authors.forename: Keqing
authors.initials: K
authors.lastname: Wang
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States 3Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Dongcheng, Beijing, China.
authors.forename: Fangtian
authors.initials: F
authors.lastname: Dong
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States 3Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States 5Structural and Computational Biology & Molecular Biophysics.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Dongcheng, Beijing, China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Sui
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D057130:Leber Congenital Amaurosis / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D010375:Pedigree; D010641:Phenotype