title: Genome-Wide Detection of Copy Number Variations in Unsolved Inherited Retinal Disease.
abstract: Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of Mendelian disorders that plays a crucial role in the etiology of blindness across the world. Molecular genetic diagnosis of IRD remains extremely complex and challenging because mutations are only detected in 40% to 60% of cases. In this study, we aimed to dissect the contributions of copy number variations (CNVs) in IRD patients.
  
  
  
  A total of 50 patients were diagnosed with IRD, all of whom previously tested negative for pathogenic mutations in known disease genes. Single-nucleotide polymorphism array analysis was performed by using the HumanCoreExome BeadChip. Analyses of CNVs were carried out by using GenomeStudio, KaryoStudio, and cnvPartition. The putative pathogenic CNVs were further confirmed by real-time quantitative PCR.
  
  
  
  We identified four novel CNVs in three different genes (one duplication in USH2A gene, two duplications in CEP290 gene, and one duplication in RIMS2 gene) in total four families, at a detection rate of 8% (4/50). All of these CNVs are currently absent in all databases. Three variations are located in genes that are already known to cause inherited retinal disease: USH2A and CEP290, while the association between mutation in the RIMS2 gene and IRD is reported for the first time.
  
  
  
  We performed whole-genome-wide CNV analyses in a large cohort as an alternative approach to molecular diagnosis of IRDs. This study dissected the contributions of CNVs of IRDs, not only increasing the yield in genetic testing but also suggesting the CNVs should be analyzed in the patients with IRDs.
authors.affiliation: Division of Ophthalmic Genetics, Lab for Stem Cell & Retinal Regeneration, Institute of Stem Cell Research, The Eye Hospital, Wenzhou Medical University, Wenzhou, China.
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Huang
authors.affiliation: Division of Ophthalmic Genetics, Lab for Stem Cell & Retinal Regeneration, Institute of Stem Cell Research, The Eye Hospital, Wenzhou Medical University, Wenzhou, China.
authors.forename: Jian-Yang
authors.initials: JY
authors.lastname: Mao
authors.affiliation: Division of Ophthalmic Genetics, Lab for Stem Cell & Retinal Regeneration, Institute of Stem Cell Research, The Eye Hospital, Wenzhou Medical University, Wenzhou, China.
authors.forename: Zhi-Qin
authors.initials: ZQ
authors.lastname: Huang
authors.affiliation: Division of Ophthalmic Genetics, Lab for Stem Cell & Retinal Regeneration, Institute of Stem Cell Research, The Eye Hospital, Wenzhou Medical University, Wenzhou, China.
authors.forename: Feng-Qin
authors.initials: FQ
authors.lastname: Rao
authors.affiliation: Division of Ophthalmic Genetics, Lab for Stem Cell & Retinal Regeneration, Institute of Stem Cell Research, The Eye Hospital, Wenzhou Medical University, Wenzhou, China.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Cheng
authors.affiliation: Division of Ophthalmic Genetics, Lab for Stem Cell & Retinal Regeneration, Institute of Stem Cell Research, The Eye Hospital, Wenzhou Medical University, Wenzhou, China.
authors.forename: Fen-Fen
authors.initials: FF
authors.lastname: Li
authors.affiliation: Division of Ophthalmic Genetics, Lab for Stem Cell & Retinal Regeneration, Institute of Stem Cell Research, The Eye Hospital, Wenzhou Medical University, Wenzhou, China.
authors.forename: Qing-Feng
authors.initials: QF
authors.lastname: Wang
authors.affiliation: Division of Ophthalmic Genetics, Lab for Stem Cell & Retinal Regeneration, Institute of Stem Cell Research, The Eye Hospital, Wenzhou Medical University, Wenzhou, China.
authors.forename: Zi-Bing
authors.initials: ZB
authors.lastname: Jin
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D056915:DNA Copy Number Variations / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012164:Retinal Diseases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; C493903:Cep290 protein, human; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C485850:RIMS3 protein, human; C112735:USH2A protein, human