Explore the vast range of titles available.

Our objective was to explore interest in genetic testing among Ashkenazi Jewish (AJ) Parkinson’s Disease (PD) cases and first-degree relatives, as genetic testing for LRRK2 G2019S is widely available. Approximately 18 % of AJ PD cases carry G2019S mutations; penetrance estimations vary between 24 and 100 % by age 80. A Genetic Attitude Questionnaire (GAQ) was administered at two New York sites to PD families unaware of LRRK2 G2019S mutation status. The association of G2019S, age, education, gender and family history of PD with desire for genetic testing (outcome) was modeled using logistic regression. One-hundred eleven PD cases and 77 relatives completed the GAQ. Both PD cases and relatives had excellent PD-specific genetic knowledge. Among PD, 32.6 % “definitely” and 41.1 % “probably” wanted testing, if offered “now.” Among relatives, 23.6 % “definitely” and 36.1 % “probably” wanted testing “now.” Desire for testing in relatives increased incrementally based on hypothetical risk of PD. The most important reasons for testing in probands and relatives were: if it influenced medication response, identifying no mutation, and early prevention and treatment. In logistic regression, older age was associated with less desire for testing in probands OR = 0.921 95%CI 0.868–0.977, p  = 0.009. Both probands and relatives express interest in genetic testing, despite no link to current treatment or prevention.

Objective Olfactory impairment is a potential marker for impending phenoconversion to Parkinson disease (PD) that may precede the development of disease by several years. Because of low specificity, it may be of greater predictive value in those with genetic mutations and its potential as a marker for developing LRRK2 PD should be evaluated. Methods We examined olfactory identification in 126 LRRK2 G2019S mutation carriers with PD, 125 mutation carriers not manifesting PD, 126 noncarriers with idiopathic PD, 106 noncarrier family members without PD, and 35 unrelated controls. We compared olfactory performance and performed mixture modeling to identify possible subgroups of olfactory performance in LRRK2 PD and nonmanifesting carriers. Results Adjusting for sex, age, cognitive score, site, and smoking history, LRRK2 PD had better olfactory scores compared to idiopathic PD (mean olfaction difference: −3.7, P < 0.001), and both LRRK2 PD and idiopathic PD had worse olfaction than controls (−12.8, −9.1, both P < 0.001). LRRK2 PD were less likely to be hyposmic than idiopathic PD (54.8% vs. 80.2%, P < 0.001). Nonmanifesting carriers and noncarrier family members did not differ. Mixture model analysis identified three classes in the LRRK2 PD and nonmanifesting carriers, suggesting that there are subgroups with poor olfactory identification in both LRRK2 PD and nonmanifesting carriers. Interpretation Therefore, olfactory identification deficit is less likely to be an obligate feature in LRRK2 PD than idiopathic PD, and while a relevant marker in some, a subset of carriers who eventually phenoconvert may proceed directly to PD without prior impaired olfaction.

To date, only one genome‐wide study has assessed the contribution of copy number variants (CNVs) to Parkinson's disease (PD). We conducted a genome‐wide scan for CNVs in a case–control dataset of Ashkenazi Jewish (AJ) origin (268 PD cases and 178 controls). Using high‐confidence CNVs, we examined the global genome wide burden of large (≥100 kb) and rare (≤1% in the dataset) CNVs between cases and controls. A total of 986 such CNVs were observed in our dataset of 432 subjects. Overall global burden analyses did not reveal significant differences between cases and controls in CNV rate, distribution of deletions or duplications or number of genes affected by CNVs. Overall deletions (total CNV size and ≥2× frequency) were found 1.4 times more often in cases than in controls (P = 0.019). The large CNVs (≥500 kb) were also significantly associated with PD (P = 0.046, 1.24‐fold higher in cases than in controls). Global burden was elevated for rare CNV regions. Specifically, for OVOS2 on Chr12p11.21, CNVs were observed only in PD cases (n = 7) but not in controls (P = 0.028) and this was experimentally validated. A total of 81 PD cases carried a rare genic CNV that was absent in controls. Ingenuity pathway analysis (IPA) identified ATXN3, FBXW7, CHCHD3, HSF1, KLC1, and MBD3 in the same disease pathway with known PD genes. We conducted a genome‐wide scan for copy number variants (CNVs) in a case–control dataset of Ashkenazi Jewish (AJ) origin (268 Parkinson's disease [PD] cases and 178 controls). Overall global burden analyses did not reveal significant differences between cases and controls in CNV rate, distribution of deletions or duplications or number of genes affected by CNVs, however deletions (total CNV size and ≥2× frequency) were found 1.4 times more often in cases than in controls (P = 0.019) and large CNVs (>500 kb) were also significantly associated with PD (P = 0.046, 1.24‐folder higher in cases than in controls). Ingenuity pathway analysis (IPA) of rare CNVs in PD cases identified ATXN3, FBXW7, CHCHD3, HSF1, KLC1, and MBD3 in the same disease pathway with known PD genes.

ObjectiveOlfactory impairment is a potential marker for impending phenoconversion to Parkinson disease (PD) that may precede the development of disease by several years. Because of low specificity, it may be of greater predictive value in those with genetic mutations and its potential as a marker for developing LRRK2 PD should be evaluated.MethodsWe examined olfactory identification in 126 LRRK2 G2019S mutation carriers with PD, 125 mutation carriers not manifesting PD, 126 noncarriers with idiopathic PD, 106 noncarrier family members without PD, and 35 unrelated controls. We compared olfactory performance and performed mixture modeling to identify possible subgroups of olfactory performance in LRRK2 PD and nonmanifesting carriers.ResultsAdjusting for sex, age, cognitive score, site, and smoking history, LRRK2 PD had better olfactory scores compared to idiopathic PD (mean olfaction difference: −3.7, P < 0.001), and both LRRK2 PD and idiopathic PD had worse olfaction than controls (−12.8, −9.1, both P < 0.001). LRRK2 PD were less likely to be hyposmic than idiopathic PD (54.8% vs. 80.2%, P < 0.001). Nonmanifesting carriers and noncarrier family members did not differ. Mixture model analysis identified three classes in the LRRK2 PD and nonmanifesting carriers, suggesting that there are subgroups with poor olfactory identification in both LRRK2 PD and nonmanifesting carriers.InterpretationTherefore, olfactory identification deficit is less likely to be an obligate feature in LRRK2 PD than idiopathic PD, and while a relevant marker in some, a subset of carriers who eventually phenoconvert may proceed directly to PD without prior impaired olfaction.

To date, only one genome‐wide study has assessed the contribution of copy number variants ( CNV s) to P arkinson's disease ( PD ). We conducted a genome‐wide scan for CNV s in a case–control dataset of A shkenazi J ewish ( AJ ) origin (268 PD cases and 178 controls). Using high‐confidence CNV s, we examined the global genome wide burden of large (≥100 kb) and rare (≤1% in the dataset) CNV s between cases and controls. A total of 986 such CNV s were observed in our dataset of 432 subjects. Overall global burden analyses did not reveal significant differences between cases and controls in CNV rate, distribution of deletions or duplications or number of genes affected by CNV s. Overall deletions (total CNV size and ≥2× frequency) were found 1.4 times more often in cases than in controls ( P  = 0.019). The large CNV s (≥500 kb) were also significantly associated with PD ( P  = 0.046, 1.24‐fold higher in cases than in controls). Global burden was elevated for rare CNV regions. Specifically, for OVOS2 on Chr12p11.21, CNV s were observed only in PD cases ( n  = 7) but not in controls ( P  =   0.028) and this was experimentally validated. A total of 81 PD cases carried a rare genic CNV that was absent in controls. Ingenuity pathway analysis ( IPA ) identified ATXN3 , FBXW7 , CHCHD3 , HSF1 , KLC1 , and MBD3 in the same disease pathway with known PD genes.

The cognitive profile of early onset Parkinson’s disease (EOPD) has not been clearly defined. Mutations in the parkin gene are the most common genetic risk factor for EOPD and may offer information about the neuropsychological pattern of performance in both symptomatic and asymptomatic mutation carriers. EOPD probands and their first-degree relatives who did not have Parkinson’s disease (PD) were genotyped for mutations in the parkin gene and administered a comprehensive neuropsychological battery. Performance was compared between EOPD probands with (N = 43) and without (N = 52) parkin mutations. The same neuropsychological battery was administered to 217 first-degree relatives to assess neuropsychological function in individuals who carry parkin mutations but do not have PD. No significant differences in neuropsychological test performance were found between parkin carrier and noncarrier probands. Performance also did not differ between EOPD noncarriers and carrier subgroups (i.e., heterozygotes, compound heterozygotes/homozygotes). Similarly, no differences were found among unaffected family members across genotypes. Mean neuropsychological test performance was within normal range in all probands and relatives. Carriers of parkin mutations, whether or not they have PD, do not perform differently on neuropsychological measures as compared to noncarriers. The cognitive functioning of parkin carriers over time warrants further study. (JINS, 2011, 17, 1–10)