Behr’s syndrome is typically associated with disturbed mitochondrial translation and mutations in the C12orf65 gene

Angela Pyle, Venkateswaran Ramesh, Marina Bartsakoulia, Veronika Boczonadi, Aurora Gomez-Duran, Agnes Herczegfalvi, Emma L. Blakely, Tania Smertenko, Jennifer Duff, Gail Eglon, David Moore, Patrick Yu Wai Man, Konstantinos Douroudis, Mauro Santibanez-Koref, Helen Griffin, Hanns Lochmüller, Veronika Karcagi, Robert W. Taylor, Patrick F. Chinnery, Rita Horvath

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11 Citations (Scopus)

Abstract

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. The first symptom in all patients was childhood-onset optic atrophy, followed by spastic paraparesis, distal weakness, motor neuropathy and ophthalmoparesis. Conclusions: We think that C12orf65 mutations are more frequent than previously suggested and screening of this gene should be considered not only in patients with mitochondrial respiratory chain deficiencies, but also in inherited peripheral neuropathies, spastic paraplegias and ataxias, especially with pre-existing optic atrophy.

Original languageEnglish
Pages (from-to)55-63
Number of pages9
JournalJournal of Neuromuscular Diseases
Volume1
Issue number1
DOIs
Publication statusPublished - 2014

Keywords

  • Ataxia
  • Behr’s syndrome
  • Mitochondrial translation
  • Optic atrophy
  • Peripheral neuropathy
  • Spastic paraplegia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Pyle, A., Ramesh, V., Bartsakoulia, M., Boczonadi, V., Gomez-Duran, A., Herczegfalvi, A., Blakely, E. L., Smertenko, T., Duff, J., Eglon, G., Moore, D., Man, P. Y. W., Douroudis, K., Santibanez-Koref, M., Griffin, H., Lochmüller, H., Karcagi, V., Taylor, R. W., Chinnery, P. F., & Horvath, R. (2014). Behr’s syndrome is typically associated with disturbed mitochondrial translation and mutations in the C12orf65 gene. Journal of Neuromuscular Diseases, 1(1), 55-63. https://doi.org/10.3233/JND-140003