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.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Hartig MB,Iuso A,Haack T,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,Krdoi
10.1016/j.ajhg.2011.09.007subject
Has Abstractpub_date
2011-10-07 00:00:00pages
543-50issue
4eissn
0002-9297issn
1537-6605pii
S0002-9297(11)00397-1journal_volume
89pub_type
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