title: Next-generation Sequencing Extends the Phenotypic Spectrum for LCA5 Mutations: Novel LCA5 Mutations in Cone Dystrophy.
abstract: We aim to characterize the clinical features and genetic causes for two affected siblings from a Chinese family with cone dystrophy (CD). Two patients and four unaffected family members were recruited and received complete ophthalmic examinations. Genomic DNA was isolated from the peripheral blood samples from all patients. Targeted next-generation sequencing (NGS) approach followed by intrafamilal cosegregation and in silico analyses were employed to determine the genetic defects. Ophthalmic evaluations finalized the clinical diagnosis of CD for the two patients in this family, both of whom presented macular atrophy with no remarkable changes in the peripheral retina. Comprehensive genetic screening approach revealed biallelic missense mutations in the Leber congenital amaurosis 5 (LCA5) gene, p.[Ala212Pro];[Tyr441Cys], as disease causative for this family. Both mutations were novel. The first substitution was predicted to eliminate a hydrogen bond and alter the tertiary structure of lebercilin, protein encoded by LCA5. We for the first time report novel biallelic LCA5 mutations in causing CD. Our study extends the phenotypic and genotypic spectrums for LCA5-associated retinopathies and better illustrates its genotype-phenotype correlations, which would help with better genetic diagnosis, prognosis, and personalized treatment for CD patients.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Chen
authors.affiliation: Ningxia Eye Hospital, People Hospital of Ningxia Hui Autonomous Region, Ningxia 750001, China.
authors.forename: Xunlun
authors.initials: X
authors.lastname: Sheng
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat Sen University, Guangzhou 510000, China.
authors.forename: Xiantao
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Ningxia Eye Hospital, People Hospital of Ningxia Hui Autonomous Region, Ningxia 750001, China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Sijia
authors.initials: S
authors.lastname: Ding
authors.affiliation: Ningxia Eye Hospital, People Hospital of Ningxia Hui Autonomous Region, Ningxia 750001, China.
authors.forename: Yani
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Ningxia Eye Hospital, People Hospital of Ningxia Hui Autonomous Region, Ningxia 750001, China.
authors.forename: Wenzhou
authors.initials: W
authors.lastname: Liu
authors.affiliation: Ningxia Eye Hospital, People Hospital of Ningxia Hui Autonomous Region, Ningxia 750001, China.
authors.forename: Zili
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.|Department of Ophthalmology, Children's Hospital of Zhengzhou, Zhengzhou, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
mesh_terms: D044466:Asian People; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005192:Family Health; D056726:Genetic Association Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics*; D020125:Mutation, Missense; D011487:Protein Conformation; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology*; D035781:Siblings
chemical_list: D005136:Eye Proteins; C522405:LCA5 protein, human; D008869:Microtubule-Associated Proteins