title: Mutation analysis in 129 genes associated with other forms of retinal dystrophy in 157 families with retinitis pigmentosa based on exome sequencing.
abstract: OBJECTIVE
  Mutations in 60 known genes were previously identified by exome sequencing in 79 of 157 families with retinitis pigmentosa (RP). This study analyzed variants in 129 genes associated with other forms of hereditary retinal dystrophy in the same cohort.
  
  
  METHODS
  Apart from the 73 genes previously analyzed, a further 129 genes responsible for other forms of hereditary retinal dystrophy were selected based on RetNet. Variants in the 129 genes determined by whole exome sequencing were selected and filtered by bioinformatics analysis. Candidate variants were confirmed by Sanger sequencing and validated by analysis of available family members and controls.
  
  
  RESULTS
  A total of 90 candidate variants were present in the 129 genes. Sanger sequencing confirmed 83 of the 90 variants. Analysis of family members and controls excluded 76 of these 83 variants. The remaining seven variants were considered to be potential pathogenic mutations; these were c.899A>G, c.1814C>G, and c.2107C>T in BBS2; c.1073C>T and c.1669C>T in INPP5E; and c.3582C>G and c.5704-5C>G in CACNA1F. Six of these seven mutations were novel. The mutations were detected in five unrelated patients without a family history, including three patients with homozygous or compound heterozygous mutations in BBS2 and INPP5E, and two patients with hemizygous mutations in CACNA1F. None of the patients had mutations in the genes associated with autosome dominant retinal dystrophy.
  
  
  CONCLUSIONS
  Only a small portion of patients with RP, about 3% (5/157), had causative mutations in the 129 genes associated with other forms of hereditary retinal dystrophy.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Guan
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xueshan
authors.initials: X
authors.lastname: Xiao
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Jia
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Guo
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yin
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Qingjiong
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D001483:Base Sequence; D020746:Calcium Channels, L-Type / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D011506:Proteins / Q000235:genetics; D058499:Retinal Dystrophies / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics*; D000099182:Phosphoinositide 5-Phosphatases
chemical_list: D020746:Calcium Channels, L-Type; D005136:Eye Proteins; D010744:Phosphoric Monoester Hydrolases; D011506:Proteins; D000099182:Phosphoinositide 5-Phosphatases; C473309:Bbs2 protein, human; C113330:CACNA1F protein, human