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author:("moho, E.S.")
1.  A comprehensive analysis of deletions, multiplications, and copy number variations in PARK2 
Neurology  2010;75(13):1189-1194.
To perform a comprehensive population genetic study of PARK2. PARK2 mutations are associated with juvenile parkinsonism, Alzheimer disease, cancer, leprosy, and diabetes mellitus, yet ironically, there has been no comprehensive study of PARK2 in control subjects; and to resolve controversial association of PARK2 heterozygous mutations with Parkinson disease (PD) in a well-powered study.
We studied 1,686 control subjects (mean age 66.1 ± 13.1 years) and 2,091 patients with PD (mean onset age 58.3 ± 12.1 years). We tested for PARK2 deletions/multiplications/copy number variations (CNV) using semiquantitative PCR and multiplex ligation-dependent probe amplification, and validated the mutations by real-time quantitative PCR. Subjects were tested for point mutations previously. Association with PD was tested as PARK2 main effect, and in combination with known PD risk factors: SNCA, MAPT, APOE, smoking, and coffee intake.
A total of 0.95% of control subjects and 0.86% of patients carried a heterozygous CNV mutation. CNV mutations found in 16 control subjects were all in exons 1–4, sparing exons that encode functionally critical protein domains. Thirteen patients had 2 CNV mutations, 5 had 1 CNV and 1 point mutation, and 18 had 1 CNV mutation. Mutations found in patients spanned exons 2–9. In whites, having 1 CNV was not associated with increased risk (odds ratio 1.05, p = 0.89) or earlier onset of PD (64.7 ± 8.6 heterozygous vs 58.5 ± 11.8 normal).
This comprehensive population genetic study in control subjects fills the void for a PARK2 reference dataset. There is no compelling evidence for association of heterozygous PARK2 mutations, by themselves or in combination with known risk factors, with PD.
= autosomal recessive juvenile parkinsonism;
= confidence interval;
= copy number variation;
= moving average plots;
= multiplex ligation-dependent probe amplification;
= NeuroGenetics Research Consortium;
= odds ratio;
= Parkinson disease.
PMCID: PMC3013490  PMID: 20876472
2.  Cognitive and motor function in long duration PARKIN PD 
JAMA neurology  2014;71(1):62-67.
The long term cognitive outcome in PARKIN-PD patients is unknown. This data may be meaningful when counseling PARKIN-PD patients.
Among early-onset PD (EOPD) patients with long disease durations, we assessed cognitive and motor performances, comparing compound heterozygote/homozygote PARKIN carriers to non-carriers
Cross sectional study
Seventeen movement disorders centers
Forty-four participants in the Consortium on Risk for Early-Onset PD (CORE-PD) with PD duration greater than median (>14 years), including PARKIN compound heterozygotes/homozygotes combined (n=21), and non-carriers (n=23).
Main outcome measures
Unified Parkinson’s Disease Rating Scale Part III (UPDRS), Clinical Dementia Rating (CDR) and neuropsychological performance. Linear regression models were applied to assess the association between PARKIN mutation status and cognitive domain scores and UPDRS. Models were adjusted for age, education, disease duration, language, and levodopa equivalent daily dose.
Compound heterozygote/homozygote PARKIN mutation carriers had earlier AAO of PD (p<0.001) and were younger (p=0.004) at time of examination than non-carriers. They performed better on the MMSE (p=0.010) and were more likely to receive lower scores on the CDR (p=0.003). In multivariate analyses, PARKIN compound heterozygotes/homozygotes performed better on the UPDRS Part III (p=0.017), and on tests of attention (p=0.022), memory (p=0.025) and visuospatial (p=0.024) domains.
Conclusions and Relevance
Cross-sectional analyses demonstrate better cognitive and motor performance in compound heterozygote/homozygote PARKIN EOPD carriers than non-carriers with long disease duration, suggesting slower disease progression. Longitudinal follow up is required to confirm these findings.
PMCID: PMC3947132  PMID: 24190026
3.  Cognitive performance of GBA mutation carriers with early-onset PD 
Neurology  2012;78(18):1434-1440.
To assess the cognitive phenotype of glucocerebrosidase (GBA) mutation carriers with early-onset Parkinson disease (PD).
We administered a neuropsychological battery and the University of Pennsylvania Smell Identification Test (UPSIT) to participants in the CORE-PD study who were tested for mutations in PARKIN, LRRK2, and GBA. Participants included 33 GBA mutation carriers and 60 noncarriers of any genetic mutation. Primary analyses were performed on 26 GBA heterozygous mutation carriers without additional mutations and 39 age- and PD duration–matched noncarriers. Five cognitive domains, psychomotor speed, attention, memory, visuospatial function, and executive function, were created from transformed z scores of individual neuropsychological tests. Clinical diagnoses (normal, mild cognitive impairment [MCI], dementia) were assigned blind to genotype based on neuropsychological performance and functional impairment as assessed by the Clinical Dementia Rating (CDR) score. The association between GBA mutation status and neuropsychological performance, CDR, and clinical diagnoses was assessed.
Demographics, UPSIT, and Unified Parkinson's Disease Rating Scale–III performance did not differ between GBA carriers and noncarriers. GBA mutation carriers performed more poorly than noncarriers on the Mini-Mental State Examination (p = 0.035), and on the memory (p = 0.017) and visuospatial (p = 0.028) domains. The most prominent differences were observed in nonverbal memory performance (p < 0.001). Carriers were more likely to receive scores of 0.5 or higher on the CDR (p < 0.001), and a clinical diagnosis of either MCI or dementia (p = 0.004).
GBA mutation status may be an independent risk factor for cognitive impairment in patients with PD.
PMCID: PMC3345785  PMID: 22442429
4.  Psychogenic movement disorders: frequency, clinical profile, and characteristics. 
Of 842 consecutive patients with movement disorders seen over a 71 month period, 28 (3.3%) were diagnosed as having a documented or clinically established psychogenic movement disorder. Tremor was most common (50%) followed by dystonia, myoclonus, and parkinsonism. Clinical descriptions of various types are reviewed. Clinical characteristics common in these patients included distractability (86%), abrupt onset (54%), and selective disabilities (39%). Distractability seems to be most important in tremor and least important in dystonia. Other diagnostic clues included entrainment of tremor to the frequency of repetitive movements of another limb, fatigue of tremor, stimulus sensitivity, and previous history of psychogenic illness. On examination, 71% had other psychogenic features. Over 60% had a clear history of a precipitating event and secondary gain and 50% had a psychiatric diagnosis (usually depression). Twenty five per cent of patients presented with combined psychogenic movement disorder and organic movement disorder; 35% resolved and this subgroup had a shorter duration of disease than those who are unresolved. Psychogenic movement disorder represents an uncommon diagnosis among patients with movement disorders. The ability to make a diagnosis rests on the presence of a multitude of clinical clues and therapeutic action should be taken as early as possible.
PMCID: PMC486078  PMID: 7561921

Results 1-4 (4)