MUTATIONS IN THE TRICARBOXYLIC ACID CYCLE ENZYME, ACONITASE 2, CAUSE EITHER ISOLATED OR SYNDROMIC OPTIC NEUROPATHY WITH ENCEPHALOPATHY AND CEREBELLAR ATROPHY

Inherited optic neuropathy can be isolated or syndromic and are associated with mutations in genes encoding proteins involved in various mitochondrial functions. We identified mutations in ACO2 encoding the mitochondrial aconitase, an enzyme of the tricarboxylic acid cycle, in five patients with optic atrophy isolated or associated with severe neurological signs. By using a yeast model we demonstrated that all these mutations were deleterious and observed a good correlation between severity of the clinical phenotype of patients and growth deficiency in yeast. These results illustrate the wide clinical expression associated with mutations in the same gene. (By Dr. Agnès Rötig, http://jmg.bmj.com/content/early/2014/10/28/jmedgenet-2014-102532 )