title: Identification of copy number variation in the gene for autosomal dominant optic atrophy, OPA1, in a Chinese pedigree.
abstract: Autosomal dominant optic atrophy (ADOA) is an optic neuropathy characterized by bilateral optic nerve pallor and decreased visual acuity. It has been reported to be associated with two genes, OPA1, OPA3, and the OPA4, OPA5, and OPA8 loci. However, mutations in OPA1 constitute the most prevalent cause of ADOA. The purpose of this study was to identify the underlying genetic defect in a Chinese pedigree with ADOA. DNA from six members of a Chinese pedigree was collected for testing genomic and copy number variation (CNV) by targeted region capture and next generation sequencing (targeted NGS). A new developmental CNV detection method was applied to analyze the sequence data. Further verification of CNV was performed by real-time polymerase chain reaction (PCR). Three members of the pedigree with clinically diagnosed ADOA were screened for pathogenic genes related to ophthalmic genetic disease. No eligible pathogenic point mutations associated with ADOA disease-causing genes were found in pedigree members with ADOA. Upon further analysis for CNVs, we found a heterozygous deletion in exons 1-9 of OPA1, which was confirmed by real-time PCR. In this study we used a new developmental method to detect CNVs associated with ADOA in a Chinese pedigree. To our knowledge, this is the first case of ADOA caused by a CNV of the OPA1 gene in Chinese patients. The findings suggest that CNVs might be an important mutation type in Chinese patients with ADOA, and that CNV screening should be performed when point mutation screens are negative in these patients.
authors.affiliation: National Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: X
authors.initials: X
authors.lastname: Jin
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Y H
authors.initials: YH
authors.lastname: Chen
authors.affiliation: National Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.affiliation: National Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Deng
authors.affiliation: National Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: N N
authors.initials: NN
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: H
authors.initials: H
authors.lastname: Huang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: M
authors.initials: M
authors.lastname: Qi
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: X
authors.initials: X
authors.lastname: Yi
authors.affiliation: National Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Chengdu, China zhujun028@163.com.
authors.forename: J
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D002681:China; D056915:DNA Copy Number Variations; D005091:Exons; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics*; D010375:Pedigree; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA / Q000379:methods; D017384:Sequence Deletion
chemical_list: D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human