Frequency of the D620N mutation in VPS35 in Parkinson disease.
OBJECTIVE
To evaluate the frequency and clinical spectrum of the recently identified p.D620N mutation in the VPS35 gene in Parkinson disease (PD) in an international sample.


METHODS
Genetic analysis by DNA sequencing and detailed clinical and neuropsychiatric assessment as well as neuroimaging in mutation carriers.


METHODS
Tertiary referral centers in Germany, Serbia, Chile, and the United States.


METHODS
One thousand seven hundred seventy-four patients with PD.


METHODS
Frequency of the p.D620N mutation.


RESULTS
A single mutation carrier was identified. The mutation carrier was a 60-year-old German man who had tremor-dominant PD since the age of 45 years. Longitudinal follow-up over 13 years revealed a disease progression from Hoehn and Yahr stage 1 to 3. There was evidence of mild cognitive impairment on the Montreal Cognitive Assessment. No abnormalities were observed by multimodal neuroimaging. He had a family history consistent with autosomal dominant inheritance. An affected paternal aunt and 3 reportedly unaffected siblings were also found to be mutation carriers.


CONCLUSIONS
VPS35 mutations are a rare cause of PD in different populations. The clinical phenotype may be indistinguishable from idiopathic PD with the possible exception of an earlier age at onset. Genetic analysis of the extended family revealed incomplete penetrance of the p.D620N mutation.
Section of Clinical and Molecular Neurogenetics, University of Lübeck, Lübeck, Germany.
Kishore R
KR
Kumar
Anne
A
Weissbach
Marcus
M
Heldmann
Meike
M
Kasten
Sinem
S
Tunc
Carolyn M
CM
Sue
Marina
M
Svetel
Vladimir S
VS
Kostić
Juan
J
Segura-Aguilar
Alfredo
A
Ramirez
David K
DK
Simon
Peter
P
Vieregge
Thomas F
TF
Münte
Johann
J
Hagenah
Christine
C
Klein
Katja
K
Lohmann
D000368:Aged; D002677:Chile; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D005858:Germany; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics*; D055771:Serbia; D062606:Tertiary Care Centers; D014481:United States; D033921:Vesicular Transport Proteins / Q000235:genetics*
C419573:VPS35 protein, human; D033921:Vesicular Transport Proteins