As Bonneau et al. (2014) correctly point out, we did describe two siblings from a non-consanguineous Norwegian family in our original Brain paper, who developed a particularly aggressive disease course characterized by ataxia, spasticity, peripheral neuropathy and myopathy (Yu-Wai-Man et al., 2010). OPA1 sequencing identified two pathogenic variants in both the affected brother and sister: the c.768C>G (p.Ser256Arg) missense mutation in exon 5b and the c.854A>G (p.Gln285Arg) missense mutation in exon 8. Bonneau et al. (2014) rightly queried whether we had actually proven compound heterozygosity in these two affected Norwegian siblings. Although DNA was not available from their deceased parents, we did have access to DNA samples from the brother’s two unaffected daughters and both harboured only the c.768C>G (p.Ser256Arg) substitution in exon 5b. Furthermore, haplotype analysis provided additional evidence that the proband and his affected sister were indeed compound heterozygous for the c.768C>G (p.Ser256Arg) and the c.854A>G (p.Gln285Arg) OPA1 mutations (Yu-Wai-Man et al., 2010).

As Bonneau et al. (2014) correctly point out, we did describe two siblings from a non-consanguineous Norwegian family in our original Brain paper, who developed a particularly aggressive disease course characterized by ataxia, spasticity, peripheral neuropathy and myopathy (Yu-Wai-Man et al., 2010). OPA1 sequencing identified two pathogenic variants in both the affected brother and sister: the c.768C>G (p.Ser256Arg) missense mutation in exon 5b and the c.854A>G (p.Gln285Arg) missense mutation in exon 8. Bonneau et al. (2014) rightly queried whether we had actually proven compound heterozygosity in these two affected Norwegian siblings. Although DNA was not available from their deceased parents, we did have access to DNA samples from the brother’s two unaffected daughters and both harboured only the c.768C>G (p.Ser256Arg) substitution in exon 5b. Furthermore, haplotype analysis provided additional evidence that the proband and his affected sister were indeed compound heterozygous for the c.768C>G (p.Ser256Arg) and the c.854A>G (p.Gln285Arg) OPA1 mutations (Yu-Wai-Man et al., 2010).