AUTHOR=Charif Majida , Roubertie Agathe , Salime Sara , Mamouni Sonia , Goizet Cyril , Hamel Christian P. , Lenaers Guy TITLE=A novel mutation of AFG3L2 might cause dominant optic atrophy in patients with mild intellectual disability JOURNAL=Frontiers in Genetics VOLUME=6 YEAR=2015 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2015.00311 DOI=10.3389/fgene.2015.00311 ISSN=1664-8021 ABSTRACT=

Dominant optic neuropathies causing fiber loss in the optic nerve are among the most frequent inherited mitochondrial diseases. In most genetically resolved cases, the disease is associated to a mutation in OPA1, which encodes an inner mitochondrial dynamin involved in network fusion, cristae structure and mitochondrial genome maintenance. OPA1 cleavage is regulated by two m-AAA proteases, SPG7 and AFG3L2, which are, respectively involved in Spastic Paraplegia 7 and Spino-Cerebellar Ataxia 28. Here, we identified a novel mutation c.1402C>T in AFG3L2, modifying the arginine 468 in cysteine in an evolutionary highly conserved arginine-finger motif, in a family with optic atrophy and mild intellectual disability. Ophthalmic examinations disclosed a loss of retinal nerve fibers on the temporal and nasal sides of the optic disk and a red–green dyschromatopsia. Thus, our results suggest that neuro-ophthalmological symptom as optic atrophy might be associated with AFG3L2 mutations, and should prompt the screening of this gene in patients with isolated and syndromic inherited optic neuropathies.