Rethinking monogenic neurological diseases

Abstract

Rethinking monogenic neurological diseases Studies on monogenic diseases can provide valuable insights into the mechanisms of other neurological disorders, say Wan-Jin Chen and colleagues This article is part of a series launched at the Chinese Stroke Association annual conference on 10 October 2020, Beijing, China. Open access fees were funded by the National Science and Technology Major Project. The BMJ peer reviewed, edited, and made the decision to publish these articles.

What is brain health and why is it important?

“…These diseases could be more readily investigated by simplified cross species modelling, leading to better understanding of their mechanisms and greater efficiency in testing innovative therapies. Such research may provide a window to promote the investigation of common neurological disorders and general brain health, as discussed by Chen and colleagues elsewhere in this series 14…”

Functional genomics and the future of iPSCs in disease modeling

“…Pathogenic mutations in one specific gene of the entire human genome can lead to monogenic disorders ( Chen et al., 2020 ). Over 10,000 monogenic diseases are known ( Chen et al., 2020 ).…”

“…Pathogenic mutations in one specific gene of the entire human genome can lead to monogenic disorders ( Chen et al., 2020 ). Over 10,000 monogenic diseases are known ( Chen et al., 2020 ). Examples include cystic fibrosis, Rett syndrome, Huntington’s disease (HD), monogenic diabetes, and polycystic kidney disease.…”

Omics Data and Their Integrative Analysis to Support Stratified Medicine in Neurodegenerative Diseases

“…The classification of NDs is still usually based on the clinical presentation (i.e., cognitive decline, speech difficulties and motor impairment), anatomical regions and cell types affected [ 1 , 2 ]. As the exact molecular mechanisms of the disease pathogenesis and progression remain unclear, the clinical management of NDs is limited to simply mitigating neurodegeneration and relieving symptoms rather than reversing the damage done [ 1 , 3 , 4 ].…”

“…NDs can be either monogenic, like Huntington disease, or complex, highly heterogeneous—including Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS)— and characterized by variable molecular phenotypes, progression courses or patterns of neuro-biochemical markers of brain damage, making patient counseling, disease management and pharmaceutical care particularly difficult [ 3 ]. The underlying mechanisms of these complex NDs are polyfactorial and depend on the combination of genetic, biological and environmental factors.…”