title: Novel compound heterozygous mutations inABCA4in a Chinese pedigree with Stargardt disease.
abstract: Stargardt disease (STGD) is a common macular dystrophy in juveniles that is commonly inherited as an autosomal recessive trait. Mutations in five genes (ABCA4,PROM1,ELOVL4,BEST1, andPRPH2) have been reported to be associated with STGD. In the present study, we aimed to identify the pathogenic mutations in affected members in a Chinese STGD pedigree.
  
  
  
  One patient was selected for whole-exome sequencing. Variants in five candidate genes were identified initially, followed by several filtering steps against public and private variation databases (1000Genomes, ESP6500si, ExAC, and in-house database), as well as bioinformatic analysis of the putative pathogenic roles. Sanger sequencing was used for cosegregation analysis among all members with available DNA.
  
  
  
  Two mutations inABCA4(NM_000350.2; c.5646G>A; p.Met1882Ile and NM_000350.2; c.3523-2A>G) were found using whole-exome sequencing. Cosegregation analysis confirmed all the affected members carried the compound heterozygous mutations while the other healthy members had at most one. The missense mutation was extremely rare in public databases and predicted to be deleterious. The splice-site mutation was absent from all public and private databases and was predicted to alter the splice pattern, resulting in an exon skip and a frameshift.
  
  
  
  Using whole-exome sequencing, we found novel compound heterozygous mutations inABCA4in a Chinese STGD pedigree. These mutations are reported for the first time, therefore widening the mutation spectrum of Stargardt disease. The present study also illustrates the potential of whole-exome sequencing in determining the genetic cause of STGD.
authors.affiliation: Department of Ophthalmology, Liuzhou Maternal and Child Healthcare Hospital, Liuzhou, Guangxi, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Graduate School of Peking Union Medical College, Beijing, China; National Research Institute of Family Planning, Beijing, China.
authors.forename: Anhui
authors.initials: A
authors.lastname: Qi
authors.affiliation: National Research Institute of Family Planning, Beijing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Graduate School of Peking Union Medical College, Beijing, China; National Research Institute of Family Planning, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Ophthalmology, Liuzhou Maternal and Child Healthcare Hospital, Liuzhou, Guangxi, China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Mo
authors.affiliation: Department of Ophthalmology, Liuzhou Maternal and Child Healthcare Hospital, Liuzhou, Guangxi, China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, Liuzhou Maternal and Child Healthcare Hospital, Liuzhou, Guangxi, China.
authors.forename: Honghui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Liuzhou Maternal and Child Healthcare Hospital, Liuzhou, Guangxi, China.
authors.forename: Zhenwen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Liuzhou Maternal and Child Healthcare Hospital, Liuzhou, Guangxi, China.
authors.forename: Meirong
authors.initials: M
authors.lastname: Wei
authors.affiliation: National Research Institute of Family Planning, Beijing, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Wang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D044466:Asian People / Q000235:genetics*; D020090:Chromosome Segregation; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008268:Macular Degeneration / Q000151:congenital* / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D000080362:Stargardt Disease; D000073359:Exome Sequencing
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters