Rita Horvath and Elke Holinski-Feder contributed equally to the study.
A new phenotype of brain iron accumulation with dystonia, optic atrophy, and peripheral neuropathy†
Version of Record online: 16 APR 2012
Copyright © 2012 Movement Disorder Society
Volume 27, Issue 6, pages 789–793, May 2012
How to Cite
Horvath, R., Holinski-Feder, E., Neeve, V. C.M., Pyle, A., Griffin, H., Ashok, D., Foley, C., Hudson, G., Rautenstrauss PhD, B., Nürnberg, G., Nürnberg, P., Kortler, J., Neitzel, B., Bäßmann, I., Rahman, T., Keavney, B., Loughlin, J., Hambleton, S., Schoser, B., Lochmüller, H., Santibanez-Koref, M. and Chinnery, P. F. (2012), A new phenotype of brain iron accumulation with dystonia, optic atrophy, and peripheral neuropathy. Mov. Disord., 27: 789–793. doi: 10.1002/mds.24980
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.
- Issue online: 30 MAY 2012
- Version of Record online: 16 APR 2012
- Manuscript Accepted: 26 FEB 2012
- Manuscript Revised: 1 FEB 2012
- Manuscript Received: 3 NOV 2011
- neurodegeneration with brain iron accumulation (NBIA);
- peripheral neuropathy;
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