title: A novel splice donor site mutation in EPHA2 caused congenital cataract in a Chinese family.
abstract: BACKGROUND
  Congenital cataract is a rare disorder characterized by crystallin denaturation, which becomes a major cause of childhood blindness. Although more than fifty pathogenic genes for congenital cataract have been reported, the genetic causes of many cataract patients remain unknown. In this study, the aim is to identify the genetic cause of a five-generation Chinese autosomal dominant congenital cataract family.
  
  
  METHODS
  Whole exome sequencing (WES) was performed on three affected and one unaffected member of the family, known causative genes were scanned first. Sanger sequencing was used to validate co-segregation of the candidate variant in the family. The impact on the transcript and amino acid sequences of the variant was further analyzed.
  
  
  RESULTS
  We identified a novel splice donor site mutation c. 2825+1G >A in EPHA2 that was absent in public and in-house databases and showed co-segregation in the family. This variant resulted in an altered splice that led to protein truncation.
  
  
  CONCLUSIONS
  The mutation we identified was responsible for congenital cataract in our studied family. Our findings broaden the spectrum of causative mutations in EPHA2 gene for congenital cataract and suggest that WES is an efficient strategy to scan variants in known causative genes for genetically heterogeneous diseases.
authors.affiliation: Department of Ophthalmology, Peking University Third Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing 100191, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Bu
authors.affiliation: BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083; BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Sijie
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Ophthalmology, Peking University Third Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing 100191, China.
authors.forename: Lejin
authors.initials: L
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Peking University Third Hospital, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing 100191, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083; The Guangdong Enterprise Key Laboratory of Human Disease Genomics, Shenzhen 518083; Shenzhen Key Laboratory of Genomics, Shenzhen 518083, China.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002386:Cataract / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D022821:RNA Splice Sites / Q000235:genetics*; D036104:Receptor, EphA2 / Q000235:genetics*; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D022821:RNA Splice Sites; D036104:Receptor, EphA2