Analysis of ATP13A2 in large neurodegeneration with brain iron accumulation (NBIA) and dystonia-parkinsonism cohorts.

Abstract

Several causative genes have been identified for both dystonia-parkinsonism and neurodegeneration with brain iron accumulation (NBIA), yet many patients do not have mutations in any of the known genes. Mutations in the ATP13A2 lead to Kufor Rakeb disease, a form of autosomal recessive juvenile parkinsonism that also features oromandibular dystonia. More recently, evidence of iron deposition in the caudate and putamen have been reported in patients with ATP13A2 mutations. We set out to determine the frequency of ATP13A2 mutations in cohorts of idiopathic NBIA and dystonia-parkinsonism. We screened for large deletions using whole genome arrays, and sequenced the entire coding region in 92 cases of NBIA and 76 cases of dystonia-parkinsonism. A number of coding and non-coding sequence variants were identified in a heterozygous state, but none were predicted to be pathogenic based on in silico analyses. Our results indicate that ATP13A2 mutations are a rare cause of both NBIA and dystonia-parkinsonism.

• Authors: Michael C Kruer, Reema Paudel, Wendy Wagoner, Lynn Sanford, Eleanna Kara, Allison Gregory, Tom Foltynie, Andrew Lees, Kailash Bhatia, John Hardy, Susan J Hayflick, Henry Houlden
• Journal: Neuroscience letters (Neurosci Lett) Vol. 523 Issue 1 Pg. 35-8 (Aug 08 2012) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 22743658 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• ATP13A2 protein, human
• Genetic Markers
• Group VI Phospholipases A2
• Proton-Translocating ATPases

Topics

• Adult
• Aged
• Aged, 80 and over
• Cohort Studies
• Comorbidity
• Dystonic Disorders (epidemiology, genetics)
• Female
• Genetic Markers (genetics)
• Genetic Predisposition to Disease (epidemiology, genetics)
• Group VI Phospholipases A2 (deficiency, genetics)
• Humans
• Internationality
• Iron Metabolism Disorders (epidemiology, genetics)
• Male
• Middle Aged
• Mutation (genetics)
• Neuroaxonal Dystrophies (epidemiology, genetics)
• Parkinsonian Disorders (epidemiology, genetics)
• Polymorphism, Single Nucleotide (genetics)
• Prevalence
• Proton-Translocating ATPases (genetics)
• Risk Factors
• Young Adult