Dataset Information

Genetic counseling and testing practices for late-onset neurodegenerative disease: a systematic review.

ABSTRACT:

Objective

To understand contemporary genetic counseling and testing practices for late-onset neurodegenerative diseases (LONDs), and identify whether practices address the internationally accepted goals of genetic counseling: interpretation, counseling, education, and support.

Methods

Four databases were systematically searched for articles published from 2009 to 2020. Peer-reviewed research articles in English that reported research and clinical genetic counseling and testing practices for LONDs were included. A narrative synthesis was conducted to describe different practices and map genetic counseling activities to the goals. Risk of bias was assessed using the Qualsyst tool. The protocol was registered with PROSPERO (CRD42019121421).

Results

Sixty-one studies from 68 papers were included. Most papers focused on predictive testing (58/68) and Huntington's disease (41/68). There was variation between papers in study design, study population, outcomes, interventions, and settings. Although there were commonalities, novel and inconsistent genetic counseling practices were identified. Eighteen papers addressed all four goals of genetic counseling.

Conclusion

Contemporary genetic counseling and testing practices for LONDs are varied and informed by regional differences and the presence of different health providers. A flexible, multidisciplinary, client- and family-centered care continues to emerge. As genetic testing becomes a routine part of care for patients (and their relatives), health providers must balance their limited time and resources with ensuring clients are safely and effectively counseled, and all four genetic counseling goals are addressed. Areas of further research include diagnostic and reproductive genetic counseling/testing practices, evaluations of novel approaches to care, and the role and use of different health providers in practice.

SUBMITTER: Crook A

PROVIDER: S-EPMC7920548 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Genetic counseling and testing practices for late-onset neurodegenerative disease: a systematic review.

Crook Ashley A Jacobs Chris C Newton-John Toby T O'Shea Rosie R McEwen Alison A

Journal of neurology 20210301 2

<h4>Objective</h4>To understand contemporary genetic counseling and testing practices for late-onset neurodegenerative diseases (LONDs), and identify whether practices address the internationally accepted goals of genetic counseling: interpretation, counseling, education, and support.<h4>Methods</h4>Four databases were systematically searched for articles published from 2009 to 2020. Peer-reviewed research articles in English that reported research and clinical genetic counseling and testing pra ...[more]

PMID: 33649871

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Project description:The pathophysiology of neurodegenerative diseases is poorly understood, and therapeutic options are few. Neurodegenerative diseases are hallmarked by progressive neuronal dysfunction and loss, associated with chronic glial and immune activation1. Microglia are the resident macrophages of the nervous system thought to be important for the clearance of debris after neuronal damage and aid to repair and regeneration. Their activation is viewed in general as a reactive process in neurodegeneration1-3. Whether microglia itself may be causative of neurodegenerative diseases is unclear. Late-onset neurodegenerative disease is frequently observed in patients with histiocytoses4-10, which are clonal myeloid diseases associated with somatic mutations in the RAS/MEK/ERK pathway such as BRAFV600E 5,11,12, suggesting a possible role of somatic mutations in neurodegeneration. Yet, expression of BRAFV600E in the hematopoietic stem cell (HSC) lineage does not cause neurodegeneration13,14. However, recent works from our laboratories and other have revealed that microglia belong to a lineage of adult tissue-resident myeloid cells that develop during organogenesis from yolk sac erythro-myeloid progenitors (EMP) distinct from HSC15-18. We thus hypothesized that somatic BRAFV600E mutations in the resident macrophage lineage may cause neurodegeneration. We found that while BRAFV600E expression in the HSC lineage causes leukemic and tumoral diseases13,14, its expression in the EMP lineage instead results in a severe late-onset neurodegenerative disorder. Neurological symptoms, neuronal death, astrogliosis, immune activation, and amyloid precursor protein deposition were driven by ERK-activated microglia clones and preventable by RAF inhibition. These results identify the fetal precursors of tissue-resident macrophages as a potential cell-of-origin for histiocytoses, and demonstrate that a somatic mutation in the EMP lineage can drive late-onset neurodegeneration. Moreover, these data identify activation of the MAP kinase pathway in microglia as a cause of neurodegenerative disease, and provide opportunities for therapeutic intervention aimed at preventing neuronal death in neurodegenerative diseases

Dataset Information

Genetic counseling and testing practices for late-onset neurodegenerative disease: a systematic review.

Objective

Methods

Results

Conclusion

Publications

Genetic counseling and testing practices for late-onset neurodegenerative disease: a systematic review.

Similar Datasets

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