Familial parkinsonism: study of original Sagamihara PARK8 (I2020T) kindred with variable clinicopathologic outcomes.
BACKGROUND
Since the causative gene linked to PARK8 parkinsonism was identified as LRRK2, LRRK2 gene mutations have been found to occur in about 4% of patients with hereditary Parkinson disease (PD); this percentage is even higher in certain populations. Moreover, no clear clinical differences between PARK8-linked parkinsonism and sporadic PD have been identified. Neuropathologic findings have been diverse in PARK8 parkinsonism, but few of the clinicopathologic examinations have been performed in the same family tree. We aimed to describe PET and neuropathologic findings in members of the same family tree with PARK8 parkinsonism.


METHODS
We conducted PET of 2 subjects and neuropathologically examined 8 subjects in the same family from the Sagamihara district, the original source of PARK8-linked parkinsonism (I2020T mutation).


RESULTS
The results of the PET scans were virtually identical to those seen in sporadic PD. The neuropathologic study results showed pure nigral degeneration with no Lewy bodies in 6 cases. One case, however, showed the presence of Lewy bodies and was similar neuropathologically to conventional PD with Lewy bodies. Another case had multiple system atrophy pathology.


CONCLUSIONS
Our study of PARK8-linked parkinsonism affecting several members of the same pedigree shows that the same gene mutation can induce diverse neuropathologies, even if the clinical picture and PET findings are virtually identical.
Hasegawa
Kazuko
K
Division of Neurology, National Hospital Organization, Sagamihara National Hospital, Japan.
Stoessl
A Jon
AJ
Yokoyama
Teruo
T
Kowa
Hisayuki
H
Wszolek
Zbigniew K
ZK
Yagishita
Saburo
S
D019797:3-Iodobenzylguanidine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007532:Isoleucine / Q000235:genetics*; D007564:Japan; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D019275:Radiopharmaceuticals; D013747:Tetrabenazine / Q000031:analogs & derivatives; D014443:Tyrosine / Q000235:genetics*
D019275:Radiopharmaceuticals; D007532:Isoleucine; C032811:dihydrotetrabenazine; D019797:3-Iodobenzylguanidine; D014443:Tyrosine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D013747:Tetrabenazine