1. For undiagnosed patients, can genetic testing directly detect or confirm the disease? In terms of testing purpose, there are two types of genetic tests, one is called diagnostic test and the other is called pre-symptomatic test. Diagnostic testing is when the patient’s symptoms are in some way consistent with the clinical manifestations of ALS, then genetic testing is usually used as an adjunct to confirm the diagnosis of the disease. A positive genetic test result is the final diagnosis. Genetic testing for people who have not yet developed symptoms is called pre-symptomatic testing. 2.What are the susceptibility genes for ALS in general? There are 29 relatively clear genes associated with ALS, but the susceptibility genes are different from the causative genes, as the susceptibility genes are all genes that may be related to the development of ALS, and there are more than 100 such genes. 3.Which genes should be tested? Genetic testing depends on the purpose of the test. For diagnostic testing, the most common pathogenic genes are usually detected. Basically, the most commonly tested genes in China are SOD1, TARDP, FUS, C90RF72, etc. These four genes are usually recommended as diagnostic tests. If the patient is younger at onset, such as 20-40 years old, testing for two other genes associated with age at onset, namely amyotrophic lateral sclerosis type II and type IV genes, is also usually recommended. If the patient not only has an early age of onset, but also conforms to the clinical manifestations of ALS, then the possibility of inheritance is greater, and testing for these two genes is also necessary to determine whether they are hereditary. 4. What is the cost of genetic testing? The cost of research and development or the type of machine purchased varies, as does the cost of the personnel involved in the test and the number of genes tested, making the fees vary from one testing facility to another. Overall, however, the cost of a genetic test averages about $1,000. Package testing is usually recommended, where multiple potentially related genes are tested at once, because some of the steps are the same for testing one gene and multiple genes, so that the average cost per gene is less. For example, testing 5 genes costs 3500 yuan, an average of 700 for one gene, while testing one gene alone may still cost more than 1000. 5.Can I directly diagnose the disease through genetic testing? Can a positive test result confirm the diagnosis and a negative test rule it out? If the test result is positive, and the detected locus belongs to the disease-causing gene after gene database comparison, then the diagnosis of ALS is definitely confirmed; if many genes are tested, or even all 29 genes are tested, even if the test result is negative, it is still impossible to determine whether it is ALS, because there are many susceptibility genes for ALS, and a negative test result does not mean that there are no other susceptibility genes causing the disease. There are many susceptibility genes for ALS. 6. What does the absence of abnormalities in the SOD1 gene test mean? Is it necessary to test for other susceptibility genes at this time? If the test result is positive, it is recommended that all relatives in the family with similar symptoms should be tested, because it is likely to be hereditary; if the test result is negative, it can only mean that the patient’s ALS is not related to the SOD1 gene, but not to the other 20 genes. If the test result is negative, it can only mean that the patient’s ALS is not related to the SOD1 gene, but not to any of the other 20 genes. 7.What is the purpose of genetic testing for patients who are already diagnosed? The term “diagnosed” refers to the clinical consideration of ALS, which is called clinical consideration or clinical diagnosis. However, since there is no specific biomarker for ALS, it is not possible to say that a positive test can confirm the diagnosis of ALS, and the only test that can confirm the diagnosis is genetic testing. Only when a positive genetic test result is found and the gene is compared in the gene pool as the causative gene, then the diagnosis is truly confirmed. Therefore, genetic testing is the basis for the final diagnosis of ALS.