Variation in GIGYF2 is not associated with
W.C. Nichols, PhD
D.K. Kissell, BS
N. Pankratz, PhD
M.W. Pauciulo, MBA
V.E. Elsaesser, BS
K.A. Clark, BS
C.A. Halter, MS
A. Rudolph, PhD
J. Wojcieszek, MD
R.F. Pfeiffer, MD
T. Foroud, PhD
For the Parkinson Study
Objective: A recent study reported that mutations in a gene on chromosome 2q36-37, GIGYF2,
result in Parkinson disease (PD). We have previously reported linkage to this chromosomal region
in a sample of multiplex PD families, with the strongest evidence of linkage obtained using the
subset of the sample having the strongest family history of disease and meeting the strictest
diagnostic criteria. We have tested whether mutations in GIGYF2 may account for the previously
observed linkage finding.
Methods: We sequenced the GIGYF2 coding region in 96 unrelated patients with PD used in our
original study that contributed to the chromosome 2q36-37 linkage signal. Subsequently, we
genotyped the entire sample of 566 multiplex PD kindreds as well as 1,447 controls to test
whether variants in GIGYF2 are causative or increase susceptibility for PD.
Results: We detected three novel variants as well as one of the previously reported seven variants
in a total of five multiple PD families; however, there was no consistent evidence that these vari-
ants segregated with PD in these families. We also did not find a significant increase in risk for PD
among those inheriting variants in GIGYF2 (p ? 0.28).
Conclusions: We believe that variation in a gene other than GIGYF2 accounts for the previously
reported linkage finding on chromosome 2q36-37. Neurology®2009;72:1886–1892
GDS ? Geriatric Depression Scale; MMSE ? Mini-Mental State Examination; NCRAD ? National Cell Repository for Alzhei-
mer’s Disease; PD ? Parkinson disease; PSG ? Parkinson Study Group; UPDRS ? Unified Parkinson’s Disease Rating Scale.
Parkinson disease (PD) is the second most common neurodegenerative disorder, affecting 3%
of the population above age 75.1Mutations in five genes can result in autosomal dominant or
autosomal recessive forms of PD.2Previously, we reported linkage to an 18 cM region on
chromosome 2q36-37 in a sample of 194 multiplex PD kindreds.3Subsequently, we demon-
strated that the evidence of linkage in this region was even greater when the dataset was limited
to the subset of pedigrees having a stronger family history of PD, typically consistent with
autosomal dominant inheritance.3,4
Within the 18-cM region identified in our linkage study, the gene for Grb10-Interacting
GYF protein 2 (GIGYF2) was identified by Giovannone and colleagues5using yeast two-
hybrid screening in a study of novel proteins linked to insulin-like growth factor receptors by
the Grb10 adapter. GIGYF2 is hypothesized to modulate IGF-I signaling.5As the IGFs and
insulin have important effects in the CNS and are potentially associated with PD,6-11the
Editorial, page 1882
Address correspondence and
reprint requests to Dr. William C.
Nichols, Division of Human
Genetics, Cincinnati Children’s
Hospital Medical Center, 3333
Burnet Avenue, Cincinnati, OH
e-Pub ahead of print on March 11, 2009, at www.neurology.org.
*The Parkinson Study Group–PROGENI Investigators are listed in the appendix.
From Cincinnati Children’s Hospital Medical Center (W.C.N., D.K.K., M.W.P., V.E.E., K.A.C.), OH; University of Cincinnati School of Medicine
(W.C.N.), OH; Indiana University Medical Center (N.P., C.A.H., J.W., T.F.), Indianapolis; University of Rochester (A.R.), NY; and University of
Tennessee Health Science Center (R.F.P.), Memphis.
Supported by R01 NS37167, MO1 RR-00750. Control samples and clinical data were provided by the National Cell Repository for Alzheimer’s
Disease (U24 AG021886) and the National Institute of Neurological Disorders and Stroke Human Genetics Resource Center DNA and Cell Line
Disclosure: The authors report no disclosures.
Medical Devices: 3730xl DNA Analyzer (Applied Biosystems, Foster City, CA).
Copyright © 2009 by AAN Enterprises, Inc.
potential involvement of GIGYF2 (also
known as TNRC15) in PD was recently inves-
tigated.12The identification of seven missense
mutations in GIGYF2 in 12 of 249 unrelated
patients with PD was reported. These muta-
tions were not observed in 227 controls.
Owing to the small size of many of the pedi-
grees and the sampling of only some of the af-
fected individuals, there were very limited data
to suggest that these mutations segregate within
these families. The goals of this study were to
characterize sequence variation within GIGYF2
in a select subset of our large sample of patients
whether any identified sequence variants in-
creased the risk for PD.
METHODS Subjects. As part of an ongoing study designed
to identify genes contributing to PD susceptibility (PROGENI
Study), subjects with PD were recruited through the Parkinson
Study Group (PSG), a network of 65 participating clinical cen-
ters located throughout North America. The inclusion criterion
was a sibling pair, both of whom were reported to have a diagno-
sis of PD or were showing signs of PD. Subjects were seen in
person by a movement disorder specialist who completed the
Unified Parkinson’s Disease Rating Scale (UPDRS) Parts II and
III,13,14the Mini-Mental State Examination (MMSE),15the Ge-
riatric Depression Scale (GDS),16and the Blessed Functional Ac-
tivity Scale.17In addition, a Diagnostic Checklist was completed,
which consists of inclusion criteria associated with autopsy con-
firmed PD as well as exclusion criteria corresponding to features
associated with other non-PD pathologic diagnoses.18Responses
on the Diagnostic Checklist were used to classify each subject
with PD as either verified PD (VPD, n ? 871), with all findings
consistent with PD, or nonverified PD (NVPD, n ? 453), with
the subject failing to meet at least one inclusion criterion or
meeting one exclusion criterion. Peripheral blood was obtained
after completion of appropriate written informed consent ap-
proved by each individual institution’s institutional review
The control sample consisted of 1,447 neurologically normal
non-Hispanic Caucasians who provided appropriate written in-
formed consent. The control samples were obtained from three
different sources: the National Cell Repository for Alzheimer’s
Disease (NCRAD), the National Institute of Neurological Dis-
orders and Stroke Human Genetics Resource Center at the Co-
riell Cell Repositories (Camden, NJ; DNA), and controls
recruited as part of an ongoing PD study at Indiana University
Molecular methods. PCR and sequencing primers were de-
signed using the chromosome 2 genomic contig sequence
NC_000002.10 enabling PCR/sequencing of all 27 coding ex-
ons and intron/exon boundaries of GIGYF2 (table e-1 on the
Neurology®Web site at www.neurology.org). PCR products
were purified and sequenced as previously described.19
TaqMan allelic-discrimination assays (Applied Biosystems,
Foster City, CA) were developed to screen for the novel missense
variants identified in the 96 sequenced samples as well as the
seven point mutations (N56S, T112A, I278V, S335T, N457T,
D606E, V1242I) previously reported.12These 10 assays were
used to genotype our complete sample of 566 PD families (with
1,497 family members, 1,324 reported to have PD), as previ-
ously described,19,20as well as the 1447 neurologically normal
non-Hispanic Caucasian control subjects (tables 1 and 2).
PCR primers were designed flanking the polyglutamine
repeat region in exon 25. The forward primer 5=-
GGAGTTTGCCAAGCAGTCC-3= and the reverse primer 5=-
TACCGCATACACCACACTAC-3= were used to amplify
DNA from ?200 PD and ?100 control subjects. The PCR
products were analyzed by electrophoresis through 4% compos-
ite agarose and visualized by ethidium bromide staining. Based
on the results of the gel electrophoresis, exon 25 PCR products
corresponding to at least six different patterns were cloned using
the TOPO Cloning Kit for Sequencing (Invitrogen, Carlsbad,
CA). DNA sequence analysis was performed on miniprep DNA
from 15 different clones from each of the cloned patterns. To
determine the frequency of each of these different alleles in all
1,497 family members (1,324 PD subjects) and 1,447 controls,
the forward primer used to PCR amplify the polyglutamine re-
Table 1 Description of 96 sequenced patients
with Parkinson disease (PD)
Age at onset, y, mean ? SD
62.0 ? 10.5
Average no. of other reported family
members with PD
Parent reported with PD (%)
Verified PD (%)
Autopsy confirmation of PD (%)
Table 2 Description of 1,324 genotyped patients with Parkinson disease (PD) and 369 controls
SourceTypeNo.Mean (range) age at onset*/
Patients with PD
Verified patients with PD
NINDS Human Genetics Resource Center (Coriell)
National Cell Repository for Alzheimer’s Disease
*Age at onset of patients with PD.
†Age at examination of controls.
NINDS ? National Institute of Neurological Disorders and Stroke.
Neurology 72June 2, 2009
gion was labeled with 6-FAM and fluorescent genotyping was
performed on a 3730xl DNA Analyzer (Applied Biosystems) and
analyzed using GeneMapper 4.0 (Applied Biosystems). Allele
counts were permuted using only one individual per family, and
?2and odds ratios were calculated separately for each allele using
these counts. Genetic association analyses were only performed
using non-Hispanic Caucasian samples (cases and controls).
RESULTS To investigate the frequency of GIGYF2
variants in familial PD, all 27 exons of GIGYF2 were
sequenced in one PD case from each of 96 different
multiplex PD families (table 1). These PD cases were
specifically selected because their families provide ev-
idence of linkage to chromosome 2q.3,4Sequencing
in the 96 index PD cases identified one subject het-
erozygous for the previously reported N56S variant
in exon 2.12We also identified one subject with each
of the following novel variants: D228E in exon 7,
K407E in exon 10, and R1195C in exon 25 (table
3). In addition, seven substitutions previously
reported as polymorphisms12were identified in
78 of the 96 index cases: P460T (rs2289912): 1
patient (reported incorrectly as P469T12); E518E
(rs2305138): 12 patients; S945S: one patient;
Q980Q (rs3816334): 65 patients; delQ1210
(rs10555297): 77 patients; P1217P (rs12328151):
41 patients; S1285S: 5 patients (table 3).
Our entire sample of 566 multiplex PD families,
consisting of 1,497 members, including 1,324 re-
ported to have PD, were genotyped for the seven
GIGYF2 point mutations previously reported12as
well as the three novel missense variants we identified
through sequencing. We identified several additional
subjects carrying GIGYF2 variants (figure 1). Among
the seven previously reported GIGYF2 variants, the
N56S variant identified in one of the 96 sequenced
patients with PD was identified in three additional
subjects: one from the same family as the subject
identified by sequencing and two in an additional
family. In family A, both siblings with verified PD
carried the N56S variant. In family B, four siblings
were initially reported to have symptoms of PD. Fol-
lowing evaluation, three of the siblings met criteria
for verified PD, while the fourth sibling did not com-
plete a study visit, but did provide a blood sample.
Among these four siblings, two carried the N56S
variant while two did not. The mother of these four
siblings provided a blood sample but was not evalu-
ated in person. She did not report any symptoms of
PD before death at age 90 and did not carry the
N56S variant. The father of these siblings died at the
age of 39 and was not reported to have any symp-
toms of PD. In this larger family, the N56S does not
segregate completely with disease. Combining our
results with those of the previous 249 subjects with
PD studied,12the N56S variant has been identified
in 0.9% (3 of 345) of unrelated PD subjects and
0.4% (6 of 1573) of all PD subjects studied.
One individual was shown to be heterozygous for
the previously reported N457T variant (family C).
This individual was evaluated at age 81 and found to
have no evidence of PD. This individual has two sib-
lings with verified PD, neither of whom carries the
variant. In addition, the individual carrying the vari-
ant also had a daughter with PD; however, she did
not carry the variant. Thus, there is no evidence that
Table 3 GIGYF2 screening
ExonNucleotide changeAmino acid change
No. of PD subjects
(no. of families) No. of controls
c.167A¡G N56S 4 (2)0
c.1219A¡G* K407E1 (1)0
c.3583C¡T*R1195C 1 (1)0
*Novel variant identified in sequencing 96 PD subjects from the families with the strongest
evidence of linkage to chromosome 2q.
†This individual did not have PD.
PD ? Parkinson disease.
Figure 1Segregation of GIGYF2 variants in pedigrees
The GIGYF2 variant identified in each family is indicated above the pedigree. To maintain
the anonymity of the pedigree, the gender of all subjects is denoted as female. PD ? Parkin-
Neurology 72June 2, 2009
the N457T variant is segregating with disease in this
We did not identify any members of our PD fam-
ilies who carried the T112A, I278V, S335T, D606E,
or V1242I variants previously identified.12While
positive controls were not available for these variants
for use in the TaqMan allelic discrimination assays,
there was 100% correlation between the sequencing
results of the 96 subjects with PD and the TaqMan
assay results for these same subjects for these five
We also genotyped our full sample for the three
novel variants identified in the 96 sequenced patients
with PD (D228E, K407E, and R1195C). The
D228E variant was found in one additional patient
with PD, the sibling of the individual in whom the
variant was first identified (family D). The affected
sibling of the individual identified by sequence anal-
ysis carrying the novel K407E variant does not carry
this variant and thus this variant does not segregate
with disease (family E). Similarly, the affected sibling
of the individual carrying the novel R1195C variant
does not carry this variant so this variant does not
seem to be segregating with PD either (family F).
While previous molecular screening has identified
causative mutations in PRKN and LRRK2 in 128
patients with PD in our patient cohort, none of
the patients with GIGYF2 variants in this report
were shown to carry either a PRKN or LRRK2
The TaqMan allelic-discrimination assays for the
10 variants previously reported12or identified in the
sequencing of patients with PD as part of this report
were also genotyped in 1,447 neurologically normal
non-Hispanic Caucasian controls.19Only one of the
10 variants genotyped (V1242I) was identified in
one control sample (table 3).
Previously, deletions and insertions in exon 25 of
GIGYF2 were reported.12To determine how many
different alleles might be represented in our study
samples, we used a combination of agarose gel elec-
trophoresis, cloning and sequencing of individual al-
leles, and fluorescent genotyping. In our analysis of
1,497 family members from 566 PD families and
1,447 neurologically normal controls, a total of eight
different alleles was observed, with six of these corre-
sponding to the six different patterns initially ob-
served by gel electrophoresis (table 4). These six
alleles ranged from a deletion of eight amino acids
(Del LPQQQQQQ 1209-1216) to an insertion of
two amino acids (Ins QQ 1217). Each of these alleles
was also previously reported.12Exon 25 PCR prod-
ucts from two individuals each heterozygous for one
of the two new alleles identified by the fluorescent
genotyping (142 and 148 bp) were subcloned and
sequenced to determine the corresponding change at
the DNA/amino acid level. Sequence analysis identi-
fied one novel allele (Del QQQQLP 1205-1210)
and one allele previously reported (Del PPQQ 1221-
1224).12Figure 2 shows the DNA sequence of the
eight alleles detected in our study. The Del
QQQQLP 1205-1210 (142 bp) allele was identified
in two siblings from a single family but not in any
controls while the Del PPQQ 1221-1224 (148 bp)
allele was detected in three controls but in none of
the PD families. Each of the other six alleles was
identified at similar frequencies in both patients with
PD and controls and there was no evidence that any
of these GIGYF2 insertion/deletions increased the
risk for PD (table 4).
DISCUSSION The goal of this study was to test
whether variants in GIGYF2 could account for the
previous evidence of linkage to chromosome
Table 4 GIGYF2 exon 25 screening
Alleles Allele size (bp) Frequency (VPD), %* Frequency (controls), %Odds ratio (p value)
160 34.234.9 0.97 (0.77)
Del Q 1210
157 56.154.61.06 (0.68)
Del PPQQ 1221-1224
Del Q 1210 ? Del PQQQ 1225-1228
1451.41.1 1.33 (0.40)
Del QQQQLP 1205-1210
Del QQQQLPQ 1205-1211
139 22.214.171.124 (0.81)
Del LPQQQQQQ 1209-1216
Del Q 1210 ? Ins QQ 1217
*Analyses were limited to non-Hispanic Caucasian individuals and only included verified Parkinson disease cases without a
causative mutation in PRKN or LRRK2 .
†The normal allele is based on the GIGYF2 sequence from chromosome 2 genomic contig sequence NC_000002.10.
‡No non-Hispanic, Caucasian individual harbored this allele.
§Odds ratio not computed when both groups had allele frequencies less than 1%.
VPD ? verified Parkinson disease.
Neurology 72June 2, 2009
2q36-37 reported in our collection of multiplex PD
families.4,23Our previous study found that a subset of
our families, in particular those with the strongest
family history of disease, provided the greatest evi-
dence of linkage to this region. Direct sequence anal-
ysis of the GIGYF2 coding region in one subject with
PD from each of 96 unrelated PD families identified
four variants (4.2%) not identified in controls (figure
2). This is similar to the 4.8% frequency previously
reported.12However, our screening of 10 variants (7
previously reported and 3 novel from this study) in
566 families yielded only 6 families with known vari-
ants (1.1%). We did not find a significant increase in
risk for PD among those inheriting variants in
GIGYF2 as compared to controls (p ? 0.28). With
the identification of so few potential mutations in
GIGYF2 in these families, it is very unlikely that
these few variants, observed in only six families (and
segregating with disease in only two families) (see
figure 1), could have accounted for the substantial
Figure 2Schematic of GIGYF2 gene (A) and amino acid/DNA sequence of GIGYF2 polymorphic exon 25 alleles (B)
(A) Schematic of GIGYF2 gene showing location of identified variants. The GIGYF2 gene structure is depicted approximately to scale with the exons
while the remaining seven were previously published. (B) Amino acid/DNA sequence of GIGYF2 polymorphic exon 25 alleles. At top is shown the amino acid
sequence corresponding to the 3= portion of exon 25 encoding residues 1200 to 1228 (numbers above amino acid sequence). Shown directly below the
amino acid sequence are the eight different alleles identified in our study sample. Numbers at left designate allele sizes (bp) by fluorescent genotyping. The
160 bp allele is the normal reference allele based on the GenBank sequence. All other alleles are shown relative to the normal 160 bp allele. Missing
residues are depicted as underlined gaps in the sequence. The QQ insertion at residue 1217 in allele 163 is indicated by the underlined CAG codons
occurring between codons 1216 and 1217 in the normal sequence.
Neurology 72June 2, 2009
linkage evidence (lod ? 5.1) reported in our sample.4
Therefore, we do not believe that variation in GI-
GYF2 accounts for the previously reported linkage
finding on chromosome 2q36-37.
Of the three novel variants identified in this study
(table 3), two of them (K407E in exon 10 and
R1195C in exon 25) represent nonconservative
amino acid substitutions which could potentially al-
ter either structure or function of GIGYF2. The
third novel variant (D228E in exon 7) would not be
predicted to interfere in protein function. Alignment
of the human GIGYF2 protein sequence with 17
other species indicate that the three variants occur
within conserved amino acid blocks and involve resi-
dues that are highly conserved across species.
While we did not detect sequence variants that
appeared consistent with a causative effect on PD, we
also explored the possibility that variation in exon 25
in GIGYF2 might increase the susceptibility or risk
of PD. The analysis of exon 25 represented a chal-
lenge due to the large number of glutamine residues
encoded in this exon. Nineteen of the final 27
codons in exon 25 encode glutamine primarily using
the CAG codon (18/19) (figure 2). The repeated
CAGs result in several different alleles that vary due
to insertions/deletions in this region and were also
observed in a previous report.12Many of the 96
samples sequenced were heterozygous for these inser-
tional/deletional events, preventing an accurate de-
termination of the sequence using conventional
direct sequence analysis of PCR products as was used
for the other exons. Several different sequence pat-
terns were noted on the chromatograms. However,
following careful delineation of all insertions and de-
letions in exon 25 using a combination of cloning/
sequencing of the individual alleles and fluorescent
genotyping, we did not detect evidence that any of
the eight observed alleles were found at higher fre-
quency in subjects with PD as compared with con-
trols (table 4). Our analysis of GIGYF2 was limited
to coding sequence alterations and would not iden-
tify dosage changes as have been identified in the
genes for parkin and ?-synuclein in some subjects
Despite careful examination of GIGYF2 to iden-
tify all sequence variation, we did not detect signifi-
cant or even suggestive evidence that variation in
GIGYF2 can cause or increase the risk of PD even
when using a cohort of samples providing evidence
of linkage to chromosome 2q36-37. Therefore, we
hypothesize that there is another gene within this
chromosome 2q region that when mutated results in
familial PD. Studies are ongoing to identify this gene
or genes. Given the increased interest in genetic test-
ing for PD, it is imperative that the pathogenicity of
any newly identified genetic variant be determined
before it is included in any panel for diagnostic test-
ing. These data should be available to the clinician to
enable proper genetic counseling, especially to those
undergoing presymptomatic testing. We urge cau-
tion in the implementation of GIGYF2 genetic test-
ing to ensure minimization of the risks of
Statistical analyses were conducted by Drs. Pankratz and Foroud.
The authors thank the subjects for their participation.
Parkinson Study Group–PROGENI Investigators: PROGENI Steering
Committee:University of Tennessee Health Science Center: R.F. Pfeiffer;
University of Rochester: F. Marshall, D. Oakes, A. Rudolph, A. Shina-
man; Columbia University Medical Center: K. Marder; Indiana Univer-
sity School of Medicine: P.M. Conneally, T. Foroud, C. Halter;
University of Kansas Medical Center: K. Lyons; Eli Lilly & Company: E.
Siemers; Medical College of Ohio: L. Elmers; University of California,
Irvine: N. Hermanowicz. PSG-PROGENI Investigators and Coordinators:
Albany Medical College: S. Factor, D. Higgins, S. Evans; Barrow Neuro-
logical Institute: H. Shill, M. Stacy, J. Danielson, L. Marlor, K. William-
son; Baylor College of Medicine: J. Jankovic, C. Hunter; Beth Israel
Deaconess Medical Center: D. Simon, P. Ryan, L. Scollins; Beth Israel
Medical Center: R. Saunders-Pullman, K. Boyar, C. Costan-Toth, E.
Ohmann; Brigham & Women’s Hospital: L. Sudarsky, C. Joubert;
Brown University (Memorial Hospital of RI): J. Friedman, K. Chou, H.
Fernandez, M. Lannon; Cleveland Clinic Florida-Weston: N. Galvez-
Jimenez, A. Podichetty, K. Thompson; Clinical Neuroscience Center: P.
Lewitt, M. DeAngelis; Colorado Neurological Institute: C. O’Brien, L.
Seeberger, C. Dingmann, D. Judd; Columbia University Medical Center:
K. Marder, J. Fraser, J. Harris; Creighton University: J. Bertoni, C. Peter-
son; Evanston Northwestern Healthcare: M. Rezak, G. Medalle; Hotel-
Dieu Hospital-Chum: S. Chouinard, M. Panisset, J. Hall, H. Poiffaut;
Hunter Homes McGuire Veterans Medical Center: V. Calabrese, P. Rob-
erge; Indiana University School of Medicine: J. Wojcieszek, J. Belden;
Institute For Neurodegenerative Disorders: D. Jennings, K. Marek, S.
Mendick; Johns Hopkins University: S. Reich, B. Dunlop; London
Health Sciences Centre: M. Jog, C. Horn; Mayo Clinic Jacksonville: R.
Uitti, M. Turk; McFarland Neurosciences: T. Ajax, J. Mannetter; Medi-
cal College of Georgia: K. Sethi, J. Carpenter, B. Dill, L. Hatch, K. Ligon,
S. Narayan; Medical College of Wisconsin: K. Blindauer, K. Abou-Samra,
J. Petit; Medical University of Ohio: L. Elmer, E. Aiken, K. Davis, C.
Schell, S. Wilson; Mount Sinai School of Medicine: M. Velickovic, W.
Koller (deceased), S. Phipps; North Shore-LIJ Health System: A. Feigin,
M. Gordon, J. Hamann, E. Licari, M. Marotta-Kollarus, B. Shannon, R.
Winnick; Northwestern University: T. Simuni, A. Videnovic, A. Kacz-
marek, K. Williams, M. Wolff; Ochsner Clinic Foundation: J. Rao, M.
Cook; Ohio State University: M. Fernandez, S. Kostyk, J. Hubble, A.
Campbell, C. Reider, A. Seward; Oregon Health & Science University: R.
Camicioli, J. Carter, J. Nutt, P. Andrews, S. Morehouse, C. Stone; Ot-
tawa Hospital Civic Site: T. Mendis, D. Grimes, C. Alcorn-Costa, P.
Gray, K. Haas, J. Vendette; Pacific Neuroscience Medical Group: J. Sut-
ton, B. Hutchinson, J. Young; Saskatoon Dist Health Board Royal Uni-
versity Hospital: A. Rajput, A. Rajput, L. Klassen, T. Shirley; Scott &
White Hospital/Texas A&M University: B. Manyam, P. Simpson, J.
Whetteckey, B. Wulbrecht; The Parkinson’s & Movement Disorder In-
stitute: D. Truong, M. Pathak, K. Frei, N. Luong, T. Tra, A. Tran, J. Vo;
Toronto Western Hospital, University Health: A. Lang, G. Kleiner-
Fisman, A. Nieves, L. Johnston, J. So; UMDNJ-School of Osteopathic
Medicine: G. Podskalny, L. Giffin; University of Alabama at Birming-
ham: P. Atchison, C. Allen; University of Alberta: W. Martin, M. Wieler;
University of Calgary: O. Suchowersky, M. Klimek; University of Califor-
Neurology 72June 2, 2009
nia Irvine: N. Hermanowicz, S. Niswonger; University of California San
Diego: C. Shults (deceased), D. Fontaine; University of California San
Francisco: M. Aminoff, C. Christine, M. Diminno, J. Hevezi; University
of Chicago: A. Dalvi, U. Kang, J. Richman, S. Uy, J. Young; University of
Cincinnati: A. Dalvi, A. Sahay, M. Gartner, D. Schwieterman; University
of Colorado Health Sciences Center: D. Hall, M. Leehey, S. Culver, T.
Derian; University of Connecticut: T. Demarcaida, S. Thurlow; Univer-
sity of Iowa: R. Rodnitzky, J. Dobson; University of Kansas Medical
Center: K. Lyons, R. Pahwa, T. Gales, S. Thomas; University of Mary-
land School of Medicine: L. Shulman, S. Reich, W. Weiner, K. Dustin;
University of Miami: K. Lyons, C. Singer, W. Koller (deceased), W.
Weiner, L. Zelaya; University of Minnesota: P. Tuite, V. Hagen, S. Ro-
landelli, R. Schacherer, J. Kosowicz; University of New Mexico: P. Gor-
don, J. Werner; University of Puerto Rico School of Medicine: C.
Serrano, S. Roque; University of Rochester: R. Kurlan, D. Berry, I.
Gardiner; University of South Florida: R. Hauser, J. Sanchez-Ramos, T.
Zesiewicz, H. Delgado, K. Price, P. Rodriguez, S. Wolfrath; University of
Tennessee Health Science Center: R. Pfeiffer, L. Davis, B. Pfeiffer; Uni-
versity of Texas Southwestern Medical Center: R. Dewey, B. Hayward, A.
Johnson, M. Meacham, B. Estes; Wake Forest University School of Med-
icine: F. Walker, V. Hunt, C. O’Neill; Washington University: B. Rac-
ette, L. Good, M. Rundle. Biostatistics and Clinical Trials Coordination
Centers Staff: A. Watts, A. Wang, T. Ross, S. Bennett, D. Kamp, E.
Julian-Baros, S. Daigneault, R. Doolan.
Received July 8, 2008. Accepted in final form December 30, 2008.
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