COMPETING FINANCIAL INTEREST The authors declare no competing financial interests.

These authors contributed equally to this work. Background—Behr’s syndrome is a classical phenotypic description of childhood-onset optic atrophy combined with various neurological symptoms, including ophthalmoparesis, nystagmus, spastic paraparesis, ataxia, peripheral neuropathy and learning difficulties. Objective—Here we describe 4 patients with the classical Behr’s syndrome phenotype from 3 unrelated families who carry homozygous nonsense mutations in the C12orf65 gene encoding a protein involved in mitochondrial translation. Methods—Whole exome sequencing was performed in genomic DNA and oxygen consumption was measured in patient cell lines. Results—We detected 2 different homozygous C12orf65 nonsense mutations in 4 patients with a homogeneous clinical presentation matching the historical description of Behr’s syndrome. Th