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Valerio Carelli, Mario Sabatelli, Rosalba Carrozzo, Teresa Rizza, Simone Schimpf, Bernd Wissinger, Claudia Zanna, Michela Rugolo, Chiara La Morgia, Leonardo Caporali, Michele Carbonelli, Piero Barboni, Caterina Tonon, Raffaele Lodi, Enrico Bertini, ‘Behr syndrome’ with OPA1 compound heterozygote mutations, Brain, Volume 138, Issue 1, January 2015, Page e321, https://doi.org/10.1093/brain/awu234
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Sir,
We have been following with great interest the developments in the field of phenotypic diversity associated with mutations in the OPA1 gene, having contributed to describe the DOA ‘plus’ phenotype in a joint effort with other groups (Amati-Bonneau et al., 2008; Hudson et al., 2008; Yu-Wai-Mann et al., 2010). A developing story concerns the increasingly recognized cases associated with OPA1 mutations presenting with a childhood onset syndrome combining optic atrophy with spastic paraplegia, cerebellar ataxia and possibly other neurological features (Yu-Wai-Mann et al., 2010; Marelli et al., 2011; Pretegiani et al., 2011; Schaaf et al., 2011). This phenotype fits the description of Behr in 1909, who presented a series of cases of ‘complicated familial optic atrophy with childhood onset’ including pyramidal signs, ataxia, posterior column sensory loss and mental retardation (Behr, 1909). While most of these cases apparently harboured heterozygous OPA1 mutations (Yu-Wai-Mann et al., 2010; Marelli et al., 2011; Pretegiani et al., 2011), the case presented by Schaaf et al. (2011) had the peculiar occurrence of compound heterozygosity for two different OPA1 mutations, the p.V903GfsX3 frameshift deletion and the p.I382M missense mutation, respectively, which suggested that bi-allelic OPA1 mutations may lead to a complicated form of optic atrophy, i.e. Behr syndrome. Most recently, Bonifert et al. (2014) further confirmed the occurrence of DOA ‘plus’ cases with bi-allelic OPA1 mutations, one of the alleles carrying the same p.I382M missense mutation.
