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A new phenotype of brain iron accumulation with dystonia, optic atrophy, and peripheral neuropathy


  • Relevant conflicts of interest/financial disclosures: Rita Horvath is supported by the Academy of Medical Sciences (UK, BH090164) and by the MRC (UK, G1000848) as part of the MRC Centre for Neuromuscular Diseases. Patrick F. Chinnery is a Wellcome Trust Senior Fellow in Clinical Science and also receives funding from the Parkinson's Disease Society (UK), the Medical Research Council Translational Muscle Centre, and the UK NIHR Biomedical Research Centre in Ageing and Age Related Disease. Bernard Keavney is supported by a BHF Personal Chair. Full financial disclosures and author roles may be found in the online version of this article.



Neurodegeneration with brain iron accumulation is clinically and genetically heterogeneous because of mutations in at least 7 nuclear genes.


We performed homozygosity mapping and whole-exome sequencing in 2 brothers with brain iron accumulation from a consanguineous family.


We identified a homozygous missense mutation in both brothers in the very recently identified chromosome 19 open-reading frame 12 gene. The disease presented before age 10 with slowly progressive tremor, dystonia, and spasticity. Additional features were optic atrophy, peripheral neuropathy, and learning difficulties. A raised serum creatine kinase indicated neuromuscular involvement, and compensatory mitochondrial proliferation implicated mitochondrial dysfunction as a pathological mechanism.


Further studies are needed to explore the function of the chromosome 19 open-reading frame 12 gene, and extended genetic analysis on larger patient cohorts will provide more information about the presentation and frequency of this disease. © 2012 Movement Disorder Society