title: Mutation survey of the optic atrophy 1 gene in 193 Chinese families with suspected hereditary optic neuropathy.
abstract: OBJECTIVE
  Dominant optic atrophy (DOA) is the most common form of autosomal inherited optic neuropathy, mainly caused by mutations in the optic atrophy 1 (OPA1) gene. The purpose of this study was to detect OPA1 gene mutations and associated phenotypes in Chinese patients with suspected hereditary optic neuropathy.
  
  
  METHODS
  A cohort of 193 Chinese families with suspected hereditary optic neuropathy was collected, which had been excluded from the three common primary mitochondrial DNA mutations associated with Leber hereditary optic neuropathy in our prior screening. Sanger sequencing was used to analyze variants in the coding and adjacent regions of OPA1.
  
  
  RESULTS
  In this study, 11 heterozygous OPA1 mutations, among which eight were novel and three were known, were identified in 12 of the 193 families (6.2%) but in none of the 192 control individuals. These novel mutations consisted of two nonsense mutations (p.E707* and p.K797*), two missense mutations (p.T330S and p.V377I), two deletions (p.S64fs and p.L331fs), one small insertion (p.L17fs), and one splice site mutation (c.2614-2A>G). Of the 12 families, three had a family history of optic neuropathy while nine were sporadic cases. Analysis of the family members in the two sporadic cases demonstrated that one parent in each of the two families had the OPA1 mutation and mild phenotype of optic atrophy. A 4-year-old boy with severe ocular phenotype was found to be compound heterozygous for two OPA1 mutations, a p.S64fs frameshift deletion and a p.V377I missense mutation, possibly implying an additive effect.
  
  
  CONCLUSIONS
  This study implies that the frequency of DOA is much lower than that of Leber hereditary optic neuropathy in Chinese compared with other ethnic groups. Lack of awareness of the mild phenotype of DOA may contribute to the low frequency of OPA1-related DOA in Chinese. The phenotype associated with compound heterozygous OPA1 mutations may suggest a possible addictive effect.
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors: Yabin
authors: Y
authors: Chen
authors: Xiaoyun
authors: X
authors: Jia
authors: Panfeng
authors: P
authors: Wang
authors: Xueshan
authors: X
authors: Xiao
authors: Shiqiang
authors: S
authors: Li
authors: Xiangming
authors: X
authors: Guo
authors: Qingjiong
authors: Q
authors: Zhang
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002675:Child, Preschool; D002681:China; D018389:Codon, Nonsense; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D020033:Protein Isoforms; D004247:DNA; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human
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