title: Novel mutations of the OPA1 gene in Chinese dominant optic atrophy.
abstract: OBJECTIVE
  To investigate OPA1 gene mutations in Chinese patients with autosomal dominant optic atrophy and sporadic optic atrophy.
  
  
  METHODS
  Molecular genetic studies and observational case series.
  
  
  METHODS
  Twenty-four patients from 10 unrelated Chinese pedigrees of autosomal-dominant optic atrophy, 35 isolated cases with bilateral optic atrophy of unknown cause, and 50 unrelated normal controls.
  
  
  METHODS
  Genomic DNA was extracted from peripheral blood leukocytes. All 28 coding exons of the OPA1 gene and flanking intron splice sites were sequenced. Putative mutations were reexamined for segregation in the respective families by direct sequencing. Further characterization of selected splicing site mutations was performed by reverse transcription-polymerase chain reaction (PCR) of each patient's leukocyte mRNA.
  
  
  METHODS
  Direct sequencing of the OPA1 gene.
  
  
  RESULTS
  Four OPA1 gene mutations were detected, including 2 splicing site mutations (c.1065+2T>C on intron 10 and c.1212+2insT on intron 12), 1 deletion (c.1776_1778delACT on exon 19), and 1 missense mutation (c.2846 T>C on exon 28). The c.1212+2insT, c.1776_1778delACT, and c.2846T>C mutations were newly identified OPA1 mutations. Reverse transcription (RT)-PCR and direct sequencing revealed that the splicing site mutations on c.1065+2T>C and c.1212+2insT caused skipping of exons 10 and 12, respectively. The c.1776_1778delACT mutation led to a deletion of the Leu amino acid on residue 593. OPA1 mutations were found in 4 of 10 familial cases (40 %) and in 1 of 35 sporadic cases of optic atrophy.
  
  
  CONCLUSIONS
  OPA1 gene mutations are causative in Chinese autosomal-dominant optic atrophy and sporadic optic atrophy. Screening for OPA1 gene mutations in patients with childhood onset optic atrophy who have no affected relatives is useful in making the diagnosis.
authors.affiliation: Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan. myyen@vghtpe.gov.tw
authors.forename: May-Yung
authors.initials: MY
authors.lastname: Yen
authors.forename: An-Guor
authors.initials: AG
authors.lastname: Wang
authors.forename: Yen-Ching
authors.initials: YC
authors.lastname: Lin
authors.forename: Ming-Ji
authors.initials: MJ
authors.lastname: Fann
authors.forename: Kwang-Jen
authors.initials: KJ
authors.lastname: Hsiao
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D002648:Child; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D009154:Mutation; D029241:Optic Atrophy, Autosomal Dominant / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D017931:DNA Primers; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human