The Dose Makes the Poison. (8th October 2021)

• Record Type: Journal Article
• Authors: Brodtmann, Amy; Huq, Aamira
• Is Part Of: Neurology. Volume 7:Number 5(2021)
• Publication Date: 2021-10-08
• Subjects: Neurogenetics -- Periodicals; 616.80442
• DOI: 10.1212/NXG.0000000000000610
• Languages: English
• ISSNs: 2376-7839

Abstract

Abstract : Most genes cause disease when the function of at least one copy of the gene is disrupted (e.g., loss-of-function mutations) or compromised (e.g., missense mutations). Gain of function, resulting from increased dose of a gene product, is a less common mechanism of disease causation. Neurologists would be familiar with Charcot-Marie-Tooth disease type 1A caused by duplications of the PMP22 gene. Gene duplications are also well known in neurodegenerative diseases, such as duplications of the amyloid precursor protein gene ( APP ), resulting in early-onset Alzheimer dementia (AD) and cerebral amyloid angiopathy (CAA), and copy number increases of the synuclein-alpha gene, SNCA, causing dementia with Lewy bodies or Parkinson disease dementia.