Complex relationship between Parkin mutations and Parkinson disease.
Mutations in the Parkin gene cause juvenile and early onset Parkinsonism. While Parkin-related disease is presumed to be an autosomal-recessive disorder, cases have been reported where only a single Parkin allele is mutated and raise the possibility of a dominant effect. In this report, we re-evaluate twenty heterozygous cases and extend the mutation screening to include the promoter and intron/exon boundaries. Novel deletion, point and intronic splice site mutations are described, along with promoter variation. These data, coupled with a complete review of published Parkin mutations, confirms that not only is recessive loss of Parkin a risk factor for juvenile and early onset Parkinsonism but that Parkin haplo-insufficiency may be sufficient for disease in some cases.
West
Andrew
A
Familial Movement Disorders, Laboratories of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.
Periquet
Magali
M
Lincoln
Sarah
S
Lücking
Christoph B
CB
Nicholl
David
D
Bonifati
Vincenzo
V
Rawal
Nina
N
Gasser
Thomas
T
Lohmann
Ebba
E
Deleuze
Jean-François
JF
Maraganore
Demetrius
D
Levey
Allan
A
Wood
Nick
N
Dürr
Alexandra
A
Hardy
John
J
Brice
Alexis
A
Farrer
Matt
M
D000293:Adolescent; D000328:Adult; D000483:Alleles; D017398:Alternative Splicing / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D008025:Ligases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012196:Review Literature as Topic; D017384:Sequence Deletion; D044767:Ubiquitin-Protein Ligases
D004247:DNA; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases