Original articleAutosomal Dominant Optic Atrophy: Penetrance and Expressivity in Patients With OPA1 Mutations
Section snippets
Subject Recruitment
Patients were recruited from different clinical centers across Australia. The study conformed to the tenets of the Helsinki Declaration, and informed consent was obtained from all participants.
Mutation Screening
DNA was collected using either buccal swab or venipuncture and was extracted using either the Puragene (Gentra Systems, Minneapolis, Minnesota, USA) or Amersham Biosciences Nucleon BACC kits (Amersham Biosciences, Piscataway, New Jersey, USA), respectively. Mutations in the OPA1 gene were screened using
Mutation Spectrum
Four hundred six affected and unaffected individuals from 17 ADOA pedigrees were recruited. OPA1 mutations had previously been reported in five of these pedigrees,13, 23 thus, only additional family members were screened for the relevant mutation. The remaining 12 pedigrees underwent full mutation screening of OPA1. Mutations were identified in six (50%) of these pedigrees. Four of these mutations had previously been reported; however, three novel mutations were identified in two families:
Discussion
In this study, a total of 17 ADOA pedigrees were recruited; however, OPA1 mutations were only identified in 11 (65%) of these. This is similar to other reports on OPA1 mutations in ADOA.10, 13, 14, 15, 23, 24, 25 These families are likely to harbor mutations in unidentified genes, and we are currently extending the number of subjects from the remaining pedigrees without OPA1 mutations to ensure suitable power for linkage analysis.15, 25, 26, 27
The clinical findings of marked intra- and
Amy C. Cohn, MBBS (Hons), is currently an Ophthalmology Registrar at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia. She completed her Master of Medicine in 2005 in the area of Autosomal Dominant Optic Atrophy. Dr Cohn was awarded the International Congress of Eye Research “Young Investigator” Award in 2004 for her work in this field. Dr Cohn interests are clinical genetics of the optic nerve and retina.
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Amy C. Cohn, MBBS (Hons), is currently an Ophthalmology Registrar at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia. She completed her Master of Medicine in 2005 in the area of Autosomal Dominant Optic Atrophy. Dr Cohn was awarded the International Congress of Eye Research “Young Investigator” Award in 2004 for her work in this field. Dr Cohn interests are clinical genetics of the optic nerve and retina.