title: A novel OPA1 mutation in a Chinese family with autosomal dominant optic atrophy.
abstract: A large four-generation Chinese family with autosomal dominant optic atrophy (ADOA) was investigated in the present study. Eight of the family members were affected in this pedigree. The affected family members exhibited early-onset and progressive visual impairment, resulting in mild to profound loss of visual acuity. The average age-at-onset was 15.9years. A new heterozygous mutation c.C1198G was identified by sequence analysis of the 12th exon of the OPA1 gene. This mutation resulted in a proline to alanine substitution at codon 400, which was located in an evolutionarily conserved region. This missense mutation in the GTPase domain was supposed to result in a loss of function for the encoded protein and act through a dominant negative effect. No other mutations associated with optic atrophy were found in our present study. The c.C1198G heterozygous mutation in the OPA1 gene may be a novel key pathogenic mutation in this pedigree with ADOA. Furthermore, additional nuclear modifier genes, environmental factors, and psychological factors may also contribute to the phenotypic variability of ADOA in this pedigree.
authors.affiliation: School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou 325027, Zhejiang, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Zhang
authors.forename: Yimin
authors.initials: Y
authors.lastname: Yuan
authors.forename: Bing
authors.initials: B
authors.lastname: Lin
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Xianning
authors.initials: X
authors.lastname: Dai
authors.forename: Huihui
authors.initials: H
authors.lastname: Zhou
authors.forename: Xujie
authors.initials: X
authors.lastname: Dong
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Liu
authors.forename: Min-Xin
authors.initials: MX
authors.lastname: Guan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People; D002681:China; D017124:Conserved Sequence; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics*; D010375:Pedigree; D055815:Young Adult
chemical_list: D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human