The parkin gene and its phenotype. Italian PD Genetics Study Group, French PD Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease.
Mutations of the parkin gene on chromosome 6 cause autosomal recessive, early onset parkinsonism. This is the most frequent form of monogenic parkinsonism so far identified. The associated phenotypical spectrum encompasses early onset, levodopa-responsive parkinsonism (average onset in the early 30s in Europe), and it overlaps with dopa-responsive dystonia in cases with the earliest onset, and with clinically typical Parkinson's disease in cases with later onset. Despite clinical features, Lewy bodies are not found at autopsy in brains of patients with parkin mutations. The parkin protein possesses ubiquitin ligase activity, which is abolished by the pathogenic mutations.
Bonifati
V
V
Department of Neurological Sciences, La Sapienza University, Rome, Italy.
De Michele
G
G
Lücking
C B
CB
Dürr
A
A
Fabrizio
E
E
Ambrosio
G
G
Vanacore
N
N
De Mari
M
M
Marconi
R
R
Capus
L
L
Breteler
M M
MM
Gasser
T
T
Oostra
B
B
Wood
N
N
Agid
Y
Y
Filla
A
A
Meco
G
G
Brice
A
A
D017668:Age of Onset; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D008025:Ligases / Q000235:genetics* / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases
D000978:Antiparkinson Agents; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases