TY - JOUR
T1 - Familial parkinsonism
T2 - Study of original Sagamihara PARK8 (I2020T) kindred with variable clinicopathologic outcomes
AU - Hasegawa, Kazuko
AU - Stoessl, A. Jon
AU - Yokoyama, Teruo
AU - Kowa, Hisayuki
AU - Wszolek, Zbigniew K.
AU - Yagishita, Saburo
N1 - Funding Information:
Z.K.W. has a potential financial interest associated with technology entitled “Identification of Mutations in PARK8, a Locus for Familial Parkinson's Disease,” Mayo Clinic case #2004-185. A patent has been issued for this technology, and it has been licensed to a commercial entity. No royalties have accrued to Z.K.W.; however, Mayo Clinic has received royalties of greater than $10,000, the federal threshold for significant financial interest, from the licensing of this technology.
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
KW - Nigral degeneration
KW - PARK8
KW - PET
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UR - http://www.scopus.com/inward/citedby.url?scp=64249149785&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2008.07.010
DO - 10.1016/j.parkreldis.2008.07.010
M3 - Article
C2 - 18804399
AN - SCOPUS:64249149785
VL - 15
SP - 300
EP - 306
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
SN - 1353-8020
IS - 4
ER -