Hartig, Monika B. and Iuso, Arcangela and Haack, Tobias and Kmiec, Tomasz and Jurkiewicz, Elzbieta and Heim, Katharina and Roeber, Sigrun and Tarabin, Victoria and Dusi, Sabrina and Krajewska-Walasek, Malgorzata and Jozwiak, Sergiusz and Hempel, Maja and Winkelmann, Juliane and Elstner, Matthias and Oexle, Konrad and Klopstock, Thomas and Mueller-Felber, Wolfgang and Gasser, Thomas and Trenkwalder, Claudia and Tiranti, Valeria and Kretzschmar, Hans and Schmitz, Gerd and Strom, Tim M. and Meitinger, Thomas and Prokisch, Holger (2011) Absence of an Orphan Mitochondrial Protein, C19orf12, Causes a Distinct Clinical Subtype of Neurodegeneration with Brain Iron Accumulation. AMERICAN JOURNAL OF HUMAN GENETICS, 89 (4). pp. 543-550. ISSN 0002-9297, 1537-6605
Full text not available from this repository. (Request a copy)Abstract
The disease classification neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of progressive neurodegenerative disorders characterized by brain iron deposits in the basal ganglia. For about half of the cases, the molecular basis is currently unknown. We used homozygosity mapping followed by candidate gene sequencing to identify a homozygous 11 bp deletion in the orphan gene C19orf12. Mutation screening of 23 ideopathic NBIA index cases revealed two mutated alleles in 18 of them, and one loss-of-function mutation is the most prevalent. We also identified compound heterozygous missense mutations in a case initially diagnosed with Parkinson disease at age 49. Psychiatric signs, optic atrophy, and motor axonal neuropathy were common findings. Compared to the most prevalent NBIA subtype, pantothenate kinase associated neurodegeneration (PKAN), individuals with two C19orf12 mutations were older at age of onset and the disease progressed more slowly. A polyclonal antibody against the predicted membrane spanning protein showed a mitochondrial localization. A histopathological examination in a single autopsy case detected Lewy bodies, tangles, spheroids, and tau pathology. The mitochondrial localization together with the immunohistopathological findings suggests a pathomechanistic overlap with common forms of neurodegenerative disorders.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENE; MUTATIONS; DYSTONIA; DISEASE; PLA2G6; PANK2; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 May 2020 05:38 |
| Last Modified: | 28 May 2020 05:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19982 |
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