With the development of second-generation sequencing technology, genetic examination is becoming more and more convenient. Simply put, second-generation sequencing technology is a means to design primers according to the corresponding genes for a patient’s possible disease and do multiple target genes at the same time to clarify the cause as much as possible in a short period of time. In the neuromuscular specialty group of neurology, muscle diseases, especially myotonic dystrophy, metabolic muscle, congenital myopathy, mitochondrial myopathy and other more common genetic diseases, and peripheral neuropathies such as peroneal muscular dystrophy, spastic paraplegia, spinal cerebellar ataxia, and familial motor neuron disease can be diagnosed by genetic testing. The disadvantage is that the cost is relatively high. However, there are many genetic companies in Beijing and Shanghai that conduct second-generation sequencing, and generally design mature sequencing packages or chips according to the disease spectrum, such as dozens of genes for limb-girdle muscular dystrophy. The sequencing knot is beneficial for both the physician and the patient. The results of genetic testing must be viewed scientifically and cannot be relied upon exclusively to diagnose disease. Clinical and laboratory tests, including muscle nerve biopsy results, take precedence over genetic testing. This requires that the physician has a solid basic skills in addition to a background in molecular biology to be able to interpret the test results correctly and not give the wrong interpretation to the patient, which affects the whole family. In particular, rare mutation loci must be treated with caution and require further validation.