Reply: Heterozygous OPA1 mutations in Behr syndrome

Abstract

Sir, We were very interested to read the fascinating clinical descriptions of two brothers who presented with childhood-onset optic atrophy and subsequently developed progressive spastic paraparesis and mild ataxia (Marelli et al ., 2010). We agree that the heterozygous c.1652G>A (p.C551Y) missense mutation in exon 17 of OPA1 is likely to be the cause of their neurological disorder, consistent with a dominant optic atrophy ‘plus’ (DOA+) phenotype. This mutation was not identified in the brothers’ mother; and the father, who is deceased, was not thought to be visually or neurologically affected. De novo OPA1 mutations are rare, accounting for <4% of all reported cases (Cohn et al ., 2007). It is therefore much more likely that the father was either non-penetrant, a phenomenon observed in up to 20% of OPA1 carriers, or visually asymptomatic, …