Behr's Syndrome is Typically Associated with Disturbed Mitochondrial Translation and Mutations in the C12orf65 Gene.


Type
Article
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Authors
Pyle, Angela 
Ramesh, Venkateswaran 
Bartsakoulia, Marina 
Boczonadi, Veronika 
Gomez-Duran, Aurora 
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.

Description
Keywords
Behr’s syndrome, ataxia, mitochondrial translation, optic atrophy, peripheral neuropathy, spastic paraplegia
Journal Title
J Neuromuscul Dis
Conference Name
Journal ISSN
2214-3599
2214-3602
Volume Title
1
Publisher
IOS Press