title: Multiethnic involvement in autosomal-dominant optic atrophy in Singapore.
abstract: PurposeAutosomal-dominant optic atrophy (ADOA), often associated with mutations in the OPA1 gene (chromosome 3q28-q29) is rarely reported in Asia. Our aim was to identify and describe this condition in an Asian population in Singapore.Patients and methodsPreliminary cross-sectional study at the Singapore National Eye Centre, including patients with clinical suspicion of ADOA, who subsequently underwent genetic testing by direct sequencing of the OPA1 gene.ResultsAmong 12 patients (10 families) with clinically suspected ADOA, 7 patients (5 families) from 3 different ethnic origins (Chinese, Indian, and Malay) carried a heterozygous pathogenic variant in the OPA1 gene. The OPA1 mutations were located on exons 8, 9, 11, and 17: c.869G>A (p.Arg290Glu), c.892A>G (p.Ser298Gly), c.1140G>A (splicing mutation), and c.1669C>T (p.Arg557*), respectively. One splicing mutation (c.871-1G>A) was identified in intron 8. We also identified a novel mutation causing optic atrophy and deafness (c.892A>G (p.Ser298Gly)). Among the phenotypic features, colour pupillometry disclosed a dissociation between low vision and preserved pupillary light reflex in ADOA.ConclusionWe report the first cases of genetically confirmed OPA1-related ADOA from Singapore, including a novel mutation causing 'ADOA plus' syndrome. Further epidemiological studies are needed in order to determine the prevalence of ADOA in South-East Asia.
authors.affiliation: Department of Neuro-Ophthalmology, Singapore National Eye Centre, Singapore, Singapore.
authors.forename: J L
authors.initials: JL
authors.lastname: Loo
authors.affiliation: Department of Neuro-Ophthalmology, Singapore National Eye Centre, Singapore, Singapore.|Singapore Eye Research Institute, Singapore, Singapore.|Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: S
authors.initials: S
authors.lastname: Singhal
authors.affiliation: Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: A V
authors.initials: AV
authors.lastname: Rukmini
authors.affiliation: Department of Neuro-Ophthalmology, Singapore National Eye Centre, Singapore, Singapore.
authors.forename: S
authors.initials: S
authors.lastname: Tow
authors.affiliation: Department of Biochemistry and Genetics, UMR CNRS6214-INSERM1083, University Hospital of Angers, Angers, France.
authors.forename: P
authors.initials: P
authors.lastname: Amati-Bonneau
authors.affiliation: Department of Biochemistry and Genetics, UMR CNRS6214-INSERM1083, University Hospital of Angers, Angers, France.
authors.forename: V
authors.initials: V
authors.lastname: Procaccio
authors.affiliation: Department of Biochemistry and Genetics, UMR CNRS6214-INSERM1083, University Hospital of Angers, Angers, France.
authors.forename: D
authors.initials: D
authors.lastname: Bonneau
authors.affiliation: Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: J J
authors.initials: JJ
authors.lastname: Gooley
authors.affiliation: Department of Biochemistry and Genetics, UMR CNRS6214-INSERM1083, University Hospital of Angers, Angers, France.
authors.forename: P
authors.initials: P
authors.lastname: Reynier
authors.affiliation: Department of Biochemistry and Genetics, UMR CNRS6214-INSERM1083, University Hospital of Angers, Angers, France.
authors.forename: M
authors.initials: M
authors.lastname: Ferré
authors.affiliation: Department of Neuro-Ophthalmology, Singapore National Eye Centre, Singapore, Singapore.|Singapore Eye Research Institute, Singapore, Singapore.|Duke-NUS Graduate Medical School, Singapore, Singapore.|Department of Biochemistry and Genetics, UMR CNRS6214-INSERM1083, University Hospital of Angers, Angers, France.
authors.forename: D
authors.initials: D
authors.lastname: Milea
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D029241:Optic Atrophy, Autosomal Dominant / Q000208:ethnology / Q000235:genetics*; D012846:Singapore; D014792:Visual Acuity
chemical_list: D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human