Khan NL, Scherfler C, Graham E, Bhatia KP, Quinn N, Lees AJ, Brooks DJ, Wood NW, Piccini P.
Dopaminergic dysfunction in unrelated, asymptomatic carriers of a single parkin mutation.
Neurology. 2005 Jan 11;64(1):134-6.
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I think this will be a well-cited paper; the authors have performed a large amount of work, 18F-dopa PET scanning of 13 apparently asymptomatic carriers of single heterozygous parkin mutations. This is not the first paper to tackle this subject but it is the most thorough. The investigators clearly show dopaminergic dysfunction in the parkin carriers and subtle extrapyramidal signs in four of the 13. The issue of pathogenicity of single heterozygous parkin mutations is one that is still unclear, and heterozygous mutations are often sold as benign, pathogenic, or somewhere between these two points in the literature, often rather arbitrarily. This presents problems both in our understanding of the etiology of parkin disease, and for genetic counselors and primary care physicians speaking with the family of parkin proven (homozygotes) PD patients. This has recently become more relevant as parkin testing is now commercially available. The data presented in this paper do not fully address the issue of pathogenicity, but they suggest that while carrying a single parkin mutation may not be sufficient to cause disease, it probably shifts the carrier closer to the threshold of a clinical manifestation of PD.