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Dan Milea, Patrizia Amati-Bonneau, Sharon Tow, Dominique Bonneau, Vincent Procaccio, Pascal Reynier, Jing Liang Loo; Multiethnic involvement in autosomal dominant optic atrophy; report of a new gene mutation causing optic atrophy and deafness. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6210.
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© ARVO (1962-2015); The Authors (2016-present)
Autosomal dominant optic atrophy (ADOA) is an ubiquitous condition causing bilateral visual loss, most commonly related to mutations in the OPA1 gene, mapped on the chromosome 3q28-q29. Despite recent data suggesting that the condition is more common than previously thought (the estimated minimum prevalence in a population in northern England is 4.07/100.000, or about 1 in 25.000), ADOA is more rarely reported in Asia. As a first step, our study aimed to detect patients with genetically confirmed ADOA in an Asian population in Singapore.
We conducted a preliminary cross-sectional study at the Singapore National Eye Centre, testing patients (using direct sequencing of the OPA1 gene) who had a clinical picture compatible with ADOA and who were seen in the outpatient clinics at our institution between January and August 2013.
We selected and tested genetically 5 patients among a series of patients with unexplained bilateral optic neuropathy, after ruling out other common causes of optic neuropathies (compression, toxic, Leber’s hereditary optic neuropathy, glaucoma, etc). Among these, 3 patients had a genetically confirmed ADOA, on exons 8 and 9: c.869G>A (p.Arg290Glu), c.871-1G>A and c.892A>G (p.Ser298Gly). Each patient belonged to 3 different families and 3 different ethnic groups: Chinese, Indian and Malay. All patients had bilateral visual loss occurring during the first two decades of life, associated with paracentral scotomas, color vision loss and optic atrophy. A positive family history of visual loss was found only in one of the patients. One proband harbored a novel heterozygous OPA1 pathogenic variant c.892A>G (p.Ser298Gly) that has not been previously catalogued in the eOPA1 database, causing optic atrophy and deafness in early childhood.
We report the first 3 families with genetically confirmed ADOA in Singapore, belonging to the three main ethnic groups of the country (Chinese, Indian, Malay). Among them, we report a new, previously undescribed mutation causing “dominant optic atrophy plus”, adding deafness to the classical phenotype of optic atrophy. Further epidemiological studies are needed in order to determine the prevalence of ADOA in Singapore.
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