Progress in gene diagnosis of amyotrophic lateral sclerosis / 中华神经科杂志

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease,for which early diagnosis is still very difficult up to now.With more and more ALS pathogenic and risk genes discovered,and especially the application of clinical trials of gene therapy in ALS,the genetic diagnosis becomes far more essential in ALS clinical practice.This presentation is a general introduction to the advantages and disadvantages of the commonly used gene detection methods,the key features of the pathogenic genes,the relationship between genotype and phenotype and the strategy of risk gene detection.The most common causative gene in Chinese ALS patients is superoxide dismutase (SOD1) gene,while in the Caucasian population is chromosome 9 open reading frame 72 (C9ORF72) gene.Familial ALS should be recommended for screening of ALS pathogenic gene panels.If negative,whole exome or genome sequencing is recommended to locate new pathogenic genes.The SOD1 and C9ORF72 should be routinely screened no matter in familial or sporadic form of ALS.In addition,if the patient has a special clinical phenotype,such as rapid or slow progression,cognitive impairment or extrapyramidal symptoms,genetic detection will be of great value for the diagnosis.