scholarly journals Presymptomatic testing of those at 25% risk of autosomal dominant neurodegenerative disease- testing team beware

2018 ◽  
Vol 27 (1) ◽  
pp. 20-21
Author(s):  
Martin B. Delatycki
Keyword(s):  
Neurodegenerative Disease ◽  
Autosomal Dominant ◽  
Presymptomatic Testing ◽  
Disease Testing

Japanese family with an autosomal dominant chromosome instability syndrome: A new neurodegenerative disease?

2000 ◽  
Vol 94 (4) ◽  
pp. 265-270 ◽  
Author(s):  
Shozo Ishikawa ◽  
Masayo Ishikawa ◽  
Takahiko Tokuda ◽  
Kunihiro Yoshida ◽  
Keiko Wakui ◽  
...  
Keyword(s):  
Neurodegenerative Disease ◽  
Autosomal Dominant ◽  
Chromosome Instability ◽  
Japanese Family

Expression of normal sequence pathogenic proteins for neurodegenerative disease contributes to disease risk: ‘permissive templating’ as a general mechanism underlying neurodegeneration

2005 ◽  
Vol 33 (4) ◽  
pp. 578-581 ◽  
Author(s):  
J. Hardy
Keyword(s):  
Neurodegenerative Disease ◽  
Autosomal Dominant ◽  
Disease Risk ◽  
Deposition Process ◽  
Pathogenic Mutation ◽  
General Mechanism ◽  
Key Factor ◽  
Dominant Disease ◽  
Jakob Disease ◽  
Two Stages

Loci underlying autosomal dominant forms of most neurodegenerative disease have been identified: prion mutations cause Gerstmann Straussler syndrome and hereditary Creutzfeldt–Jakob disease, tau mutations cause autosomal dominant frontal temporal dementia and α-synuclein mutations cause autosomal dominant Parkinson's disease. In these cases, the pathogenic mutation is in the protein that is deposited in the diseased tissue and the whole protein is deposited. In Alzheimer's disease, mutations in amyloid precursor protein or in the presenilins cause autosomal dominant disease. These are the substrate and proteases responsible for the production of the deposited peptide Aβ. Thus, in all the cases, the mutations lead to the disease by a mechanism that involves the deposition process. Furthermore, sporadic forms of all these diseases are predisposed by genetic variability at the same loci, implying that the quantity of the normal protein influences the risk of this form of disease. These results show that the amount of pathogenic protein expression is a key factor in determining disease initiation. Recent work on transgenic models of these diseases is consistent with the view that there are two stages of pathogenesis: a concentration-dependent formation of a pathogenic protein oligomer followed by aggregation on to this oligomeric template by a process that is less dependent on the concentration of the protein.

scholarly journals Revisiting the neuropsychiatry of Huntington's disease

2016 ◽  
Vol 10 (4) ◽  
pp. 261-266 ◽  
Author(s):  
Antonio Lucio Teixeira ◽  
Leonardo Cruz de Souza ◽  
Natalia Pessoa Rocha ◽  
Erin Furr-Stimming ◽  
Edward C. Lauterbach
Keyword(s):  
Cognitive Impairment ◽  
Neurodegenerative Disease ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Functional Capacity ◽  
Autosomal Dominant ◽  
Neuropsychiatric Symptoms ◽  
Executive Dysfunction ◽  
Behavioral Symptoms ◽  
Motor Symptoms

ABSTRACT Huntington's disease (HD) is an autosomal dominant neurodegenerative disease classified under the choreas. Besides motor symptoms, HD is marked by cognitive and behavioral symptoms, impacting patients' functional capacity. The progression of cognitive impairment and neuropsychiatric symptoms occur in parallel with neurodegeneration. The nature of these symptoms is very dynamic, and the major clinical challenges include executive dysfunction, apathy, depression and irritability. Herein, we provide a focused updated review on the cognitive and psychiatric features of HD.

Attitudes of at-risk and affected individuals regarding presymptomatic testing for autosomal dominant polycystic kidney disease

1990 ◽  
Vol 35 (4) ◽  
pp. 510-515 ◽  
Author(s):  
Eva Sujansky ◽  
Susan Beeler Kreutzer ◽  
Ann M. Johnson ◽  
Dennis C. Lezotte ◽  
Robert W. Schrier ◽  
...  
Keyword(s):  
At Risk ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Presymptomatic Testing ◽  
Autosomal Dominant Polycystic Kidney

Genetics of Neurodegenerative Diseases

2016 ◽  
Author(s):  
Lynn M. Bekris ◽  
James B. Leverenz
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Neurodegenerative Disorders ◽  
Genetic Variants ◽  
Dementia With Lewy Bodies ◽  
Autosomal Dominant ◽  
Lewy Bodies ◽  
Genetic Knowledge ◽  
Dominant Mutation ◽  
Time Line

A great deal has been discovered about Neurodegenerative disorders (NDDs) including Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, dementia with Lewy bodies . This includes genetic variants associated with both sporadic and autosomal dominant NDDs. These findings have been crucial in our understanding the underlying factors that drive neuropathological changes and in clarifying the time line of biomarker changes in presymptomatic autosomal dominant mutation carriers. While much is still to be learned, these findings will play an important role in the future of neurodegenerative prediction, diagnosis, and treatment. This chapter summarizes the current genetic knowledge related to both the sporadic and autosomal dominant forms of neurodegenerative disease.

scholarly journals ‘A sword of Damocles’: patient and caregiver beliefs, attitudes and perspectives on presymptomatic testing for autosomal dominant polycystic kidney disease: a focus group study

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e038005
Author(s):  
Charlotte Logeman ◽  
Yeoungjee Cho ◽  
Benedicte Sautenet ◽  
Gopala K Rangan ◽  
Talia Gutman ◽  
...  
Keyword(s):  
Decision Making ◽  
Family Planning ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Financial Burden ◽  
Well Being ◽  
Polycystic Kidney ◽  
Presymptomatic Testing ◽  
Autosomal Dominant Polycystic Kidney

Background and objectivesPresymptomatic testing is available for early diagnosis of hereditary autosomal dominant polycystic kidney disease (ADPKD). However, the complex ethical and psychosocial implications can make decision-making challenging and require an understanding of patients’ values, goals and priorities. This study aims to describe patient and caregiver beliefs and expectations regarding presymptomatic testing for ADPKD.Design, setting and participants154 participants (120 patients and 34 caregivers) aged 18 years and over from eight centres in Australia, France and Korea participated in 17 focus groups. Transcripts were analysed thematically.ResultsWe identified five themes: avoiding financial disadvantage (insecurity in the inability to obtain life insurance, limited work opportunities, financial burden); futility in uncertainty (erratic and diverse manifestations of disease limiting utility, taking preventive actions in vain, daunted by perplexity of results, unaware of risk of inheriting ADPKD); lacking autonomy and support in decisions (overwhelmed by ambiguous information, medicalising family planning, family pressures); seizing control of well-being (gaining confidence in early detection, allowing preparation for the future, reassurance in family resilience); and anticipating impact on quality of life (reassured by lack of symptoms, judging value of life with ADPKD).ConclusionsFor patients with ADPKD, presymptomatic testing provides an opportunity to take ownership of their health through family planning and preventive measures. However, these decisions can be wrought with tensions and uncertainty about prognostic implications, and the psychosocial and financial burden of testing. Healthcare professionals should focus on genetic counselling, mental health and providing education to patients’ families to support informed decision-making. Policymakers should consider the cost burden and risk of discrimination when informing government policies. Finally, patients are recommended to focus on self-care from an early age.

scholarly journals The Retromer Complex protein VPS35 Modulates Iron Homeostasis by Regulating Hepcidin-induced Ferroportin Degradation

2018 ◽  
Author(s):  
Zinger Yang
Keyword(s):  
Cell Surface ◽  
Functional Genomics ◽  
Neurodegenerative Disease ◽  
Iron Homeostasis ◽  
Autosomal Dominant ◽  
Underlying Mechanism ◽  
Iron Accumulation ◽  
Retromer Complex ◽  
Complex Protein ◽  
Important Regulator

Hepcidin-mediated degradation of the iron exporter Ferroportin is an essential mechanism for iron homeostasis. Upon Hepcidin binding to the Ferroportin receptor at the cell surface, Ferroportin is rapidly internalized and degraded. However, the underlying mechanism for the degradation has not been uncovered. Using a functional genomics approach, VPS35, a member of the Retromer Complex, is identified as an important regulator for Hepcidin-induced Ferroportin degradation. Cells with CRISPR- induced mutation in VPS35 demonstrated significantly reduced Ferroportin degradation in the presence of Hepcidin. Interestingly, VPS35 mutations and dysfunction of other members of the Retromer Complex have been associated with familial autosomal- dominant Parkinson’s disease, a progressive neurodegenerative disease with well- established iron accumulation phenotype. The result of this study reveals a previously unappreciated role for the Retromer Complex in the regulation of iron homeostasis.

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