Journal Article

The genetics and neuropathology of amyotrophic lateral sclerosis

Jones, Ashley, King, Andrew, Al-Chalabi, Ammar, Al-Sarraj, Safa, van den Berg, Leonard H., Troakes, Claire

2012

Overview

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons leading to death from respiratory failure within about 3 years of symptom onset. A family history of ALS is obtained in about 5 % but the distinction between familial and apparently sporadic ALS is artificial and genetic factors play a role in all types. For several years, only one gene was known to have a role in ALS pathogenesis, SOD1 . In the last few years there has been a rapid advance in our genetic knowledge of the causes of ALS, and the relationship of the genetic subtypes with pathological subtypes and clinical phenotype. Mutations in the gene for TDP-43 protein, TARDBP , highlight this, with pathology mimicking closely that found in other types of ALS, and a phenotypic spectrum that includes frontotemporal dementia. Mutations in the FUS gene, closely related to TDP-43, lead to a similar clinical phenotype but distinct pathology, so that the three pathological groups represented by SOD1 , TARDBP , and FUS are distinct. In this review, we explore the genetic architecture of ALS, highlight some of the genes implicated in pathogenesis, and describe their phenotypic range and overlap with other diseases.

• Publisher: Springer-Verlag,Springer,Springer Nature B.V
• Subject: Amyotrophic lateral sclerosis / Amyotrophic Lateral Sclerosis - genetics / Amyotrophic Lateral Sclerosis - pathology / Dementia / Disease / DNA-Binding Proteins - genetics / Family medical history / Frontotemporal dementia / Frontotemporal Dementia - genetics / Frontotemporal Dementia - pathology / FUS gene / FUS protein / Genes / Genetic factors / Genetic Predisposition to Disease / Genetics / Genotype & phenotype / Humans / Medicine / Medicine & Public Health / Mimicry / Motor neurons / Motor Neurons - pathology / Mutation / Nervous system diseases / Neurodegenerative diseases / Neuropathology / Neurosciences / Pathogenesis / Pathology / Respiration / Respiratory failure / Review / Superoxide dismutase / Superoxide Dismutase - genetics / Superoxide Dismutase-1