1. A novel OPA1 mutation in a Chinese family with autosomal dominant optic atrophy
- Author
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Xujie Dong, Min-Xin Guan, Hao Feng, Huihui Zhou, Bing Lin, Yan Li, Xiaoling Liu, Juanjuan Zhang, Xianning Dai, and Yimin Yuan
- Subjects
Adult ,Male ,China ,Mitochondrial DNA ,Adolescent ,Sequence analysis ,Molecular Sequence Data ,Biophysics ,Biology ,Biochemistry ,GTP Phosphohydrolases ,Young Adult ,Exon ,Atrophy ,Asian People ,Optic Atrophy, Autosomal Dominant ,medicine ,Animals ,Humans ,Missense mutation ,Amino Acid Sequence ,Molecular Biology ,Gene ,Conserved Sequence ,Loss function ,Aged ,Genetics ,Cell Biology ,Middle Aged ,medicine.disease ,eye diseases ,Pedigree ,Mutation ,Mutation (genetic algorithm) ,Female - Abstract
Highlights: Black-Right-Pointing-Pointer We report the characterization of a four-generation large Chinese family with ADOA. Black-Right-Pointing-Pointer We find a new heterozygous mutation c.C1198G in OPA1 gene which may be a novel pathogenic mutation in this pedigree. Black-Right-Pointing-Pointer We do not find any mitochondrial DNA mutations associated with optic atrophy. Black-Right-Pointing-Pointer Other factors may also contribute to the phenotypic variability of ADOA in this pedigree. -- 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 15.9 years. 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 inmore » 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.« less
- Published
- 2012