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Hartig, M.B. ; Iuso, A. ; Haack, T.B. ; Kmiec, T.* ; Jurkiewicz, E.* ; Heim, K. ; Roeber, S.* ; Tarabin, V.* ; Dusi, S.* ; Krajewska-Walasek, M.* ; Jozwiak, S.* ; Hempel, M. ; Winkelmann, J. ; Elstner, M. ; Oexle, K.* ; Klopstock, T.* ; Mueller-Felber, W.* ; Gasser, T.* ; Trenkwalder, C.* ; Tiranti, V.* ; Kretzschmar, H.* ; Schmitz, G.* ; Strom, T.M. ; Meitinger, T. ; Prokisch, H.

Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation.

Am. J. Hum. Genet. 89, 543-550 (2011)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Gene; Mutations; Dystonia; Disease; PLA2G6; PANK2
ISSN (print) / ISBN 0002-9297
e-ISSN 1537-6605
Journal American Journal of Human Genetics, The
Quellenangaben Volume: 89, Issue: 4, Pages: 543-550 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)