Browsing by Author "Hattori, Nobutaka"

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    Genetic Testing in Parkinson's Disease
    (Wiley, 2023) Pal, Gian; Cook, Lola; Schulze, Jeanine; Verbrugge, Jennifer; Alcalay, Roy N.; Merello, Marcelo; Sue, Carolyn M.; Bardien, Soraya; Bonifati, Vincenzo; Chung, Sun Ju; Foroud, Tatiana; Gatto, Emilia; Hall, Anne; Hattori, Nobutaka; Lynch, Tim; Marder, Karen; Mascalzoni, Deborah; Novaković, Ivana; Thaler, Avner; Raymond, Deborah; Salari, Mehri; Shalash, Ali; Suchowersky, Oksana; Mencacci, Niccolò E.; Simuni, Tanya; Saunders-Pullman, Rachel; Klein, Christine; Medical and Molecular Genetics, School of Medicine
    Genetic testing for persons with Parkinson's disease is becoming increasingly common. Significant gains have been made regarding genetic testing methods, and testing is becoming more readily available in clinical, research, and direct-to-consumer settings. Although the potential utility of clinical testing is expanding, there are currently no proven gene-targeted therapies, but clinical trials are underway. Furthermore, genetic testing practices vary widely, as do knowledge and attitudes of relevant stakeholders. The specter of testing mandates financial, ethical, and physician engagement, and there is a need for guidelines to help navigate the myriad of challenges. However, to develop guidelines, gaps and controversies need to be clearly identified and analyzed. To this end, we first reviewed recent literature and subsequently identified gaps and controversies, some of which were partially addressed in the literature, but many of which are not well delineated or researched. Key gaps and controversies include: (1) Is genetic testing appropriate in symptomatic and asymptomatic individuals without medical actionability? (2) How, if at all, should testing vary based on ethnicity? (3) What are the long-term outcomes of consumer- and research-based genetic testing in presymptomatic PD? (4) What resources are needed for clinical genetic testing, and how is this impacted by models of care and cost-benefit considerations? Addressing these issues will help facilitate the development of consensus and guidelines regarding the approach and access to genetic testing and counseling. This is also needed to guide a multidisciplinary approach that accounts for cultural, geographic, and socioeconomic factors in developing testing guidelines.
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    International Genetic Testing and Counseling Practices for Parkinson's Disease
    (Wiley, 2023) Saunders-Pullman, Rachel; Raymond, Deborah; Ortega, Roberto A.; Shalash, Ali; Gatto, Emilia; Salari, Mehri; Markgraf, Maggie; Alcalay, Roy N.; Mascalzoni, Deborah; Mencacci, Niccolò E.; Bonifati, Vincenzo; Merello, Marcelo; Chung, Sun Ju; Novakovic, Ivana; Bardien, Soraya; Pal, Gian; Hall, Anne; Hattori, Nobutaka; Lynch, Timothy; Thaler, Avner; Sue, Carolyn M.; Foroud, Tatiana; Verbrugge, Jennifer; Schulze, Jeanine; Cook, Lola; Marder, Karen; Suchowersky, Oksana; Klein, Christine; Simuni, Tatyana; Medical and Molecular Genetics, School of Medicine
    Background: There is growing clinical and research utilization of genetic testing in Parkinson's disease (PD), including direct-to-consumer testing. Objectives: The aim is to determine the international landscape of genetic testing in PD to inform future worldwide recommendations. Methods: A web-based survey assessing current practices, concerns, and barriers to genetic testing and counseling was administered to the International Parkinson and Movement Disorders Society membership. Results: Common hurdles across sites included cost and access to genetic testing, and counseling, as well as education on genetic counseling. Region-dependent differences in access to and availability of testing and counseling were most notable in Africa. High-income countries also demonstrated heterogeneity, with European nations more likely to have genetic testing covered through insurance than Pan-American and Asian countries. Conclusions: This survey highlights not only diversity of barriers in different regions but also the shared and highly actionable needs for improved education and access to genetic counseling and testing for PD worldwide. © 2023 International Parkinson and Movement Disorder Society.
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    Novel Variants in the CLCN1, RYR2, and DCTN1 Found in Elderly Japanese Dementia Patients: A Case Series
    (MDPI, 2021-02-07) Hori, Atsushi; Ai, Tomohiko; Isshiki, Miwa; Motoi, Yumiko; Yano, Kouji; Tabe, Yoko; Hattori, Nobutaka; Miida, Takashi; Medicine, School of Medicine
    Dementia has an enormous impact on medical and financial resources in aging societies like Japan. Diagnosis of dementia can be made by physical and mental examinations, imaging tests, and findings of high abnormal proteins in cerebrospinal fluids. In addition, genetic tests can be performed in neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia (FTD), and Parkinson's disease (PD). In this case series, we presented three cases of dementia with unknown causes who carry novel variants in the genes associated with neurodegenerative diseases. Three patients (Patients 1, 2, and 6) were found by screening 18 dementia patients using a gene panel including 63 genes. The age of onset for Patient 1 was 74 years old, and his father had PD and mother had AD. The age of onset for Patient 2 was 75 years old, and her mother had AD. The age of onset for Patient 6 was 83 years old, and her father, two sisters, and daughter had dementia. The Mini-Mental State Examination produced results of 20, 15, and 22, respectively. The suspected diagnosis by neurological examinations and imaging studies for Patients 1 and 2 was AD, and for Patient 6 was FTD. Patient 1 was treated with donepezil; Patient 2 was treated with donepezil and memantine; and Patient 6 was treated with donepezil, galantamine, and rivastigmine. The three rare variants identified were: CLCN1, encoding a chloride channel, c.2848G>A:p.Glu950Lys (Patient 1); RYR2, encoding a calcium releasing ryanodine receptor, c.13175A>G:p.Lys4392Arg (Patient 2); and DCTN1, encoding a subunit of dynactin, c. 3209G>A:p.Arg1070Gln (Patient 6). The detected variants were interpreted according to the American College of Medical Genetics (ACMG) guidelines. The minor allele frequency for each variant was 0.025%, 0.023%, and 0.0004% in East Asians, respectively. The DCTN1 variant found in Patient 6 might be associated with FTD. Although none of them were previously reported in dementia patients, all variants were classified as variants of unknown significance (VUS). Our report suggests that results of genetic tests in elderly patients with dementia need to be carefully interpreted. Further data accumulation of genotype-phenotype relationships and development of appropriate functional models are warranted.