title: Mutation screening of mitochondrial DNA as well as OPA1 and OPA3 in a Chinese cohort with suspected hereditary optic atrophy.
abstract: OBJECTIVE
  Leber's hereditary optic atrophy (LHON) and autosomal dominant optic atrophy (DOA) are the two most common forms. The objective of this study was to define the fractional prevalence of LHON and DOA in a cohort of Chinese patients with suspected hereditary optic neuropathy.
  
  
  METHODS
  We recruited 520 unrelated patients with bilateral optic atrophy for genetic analysis: 174 patients had a positive family history of visual failure and 346 were sporadic cases. A total of 14 primary LHON-causing mtDNA mutations was screened by PCR-based sequencing methods for all patients except the individuals with a paternal family history. All coding exons and exon-intron boundaries of the OPA1 and OPA3 gene were screened for mutations by PCR-based DNA sequencing for all patients with paternal family history and for the LHON-negative patients. A large genomic DNA arrangement of the OPA1 gene was detected further by multiplex ligation probe amplification (MLPA) assay for the patients with paternal family history, but results were negative for the OPA1 and OPA3 mutation screenings.
  
  
  RESULTS
  We found molecular defects in 323 (62%) of the 520 probands screened. Among these, 271 patients (83.9%) had an mtDNA mutation, 50 patients (15.5%) carried an OPA1 mutation, and 2 patients (0.6%) had an OPA3 mutation. Coexistence m.3460 G>A and m.11778G>A was found in one patient. We identified 40 intragenic mutations and six large genomic DNA arrangements of the OPA1 gene, 23 of which were novel.
  
  
  CONCLUSIONS
  The LHON-mtDNA mutations are the most common genetic defects, followed by the OPA1 mutations, in this Chinese cohort.
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Dong
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Yanfan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
mesh_terms: D044466:Asian People / Q000235:genetics*; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005091:Exons; D005500:Follow-Up Studies; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D015418:Optic Atrophies, Hereditary / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D004272:DNA, Mitochondrial; C443108:OPA3 protein, human; D011506:Proteins; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human
keywords: ADOA; LHON; OPA1; OPA3; mtDNA