Genetics of Charcot-Marie-Tooth Dystrophy and Related Diseases

[Background] Peroneal muscular atrophy (Charcot-Marie-Tooth, CMT) is a group of the most common hereditary peripheral neuropathy, with a prevalence of about 1/2500-4000. The inheritance mode can be autosomal dominant inheritance, autosomal recessive inheritance, X-linked dominant inheritance and X-linked recessive inheritance. The typical clinical manifestations are progressive, length-dependent weakness and atrophy of the distal limbs, accompanied by hypoesthesia and weakened tendon reflexes. But the generalized peroneal muscular atrophy also includes hereditary motor neuropathy and hereditary sensory neuropathy, which represents the evolution of a disease spectrum from motor nerve to motor sensory nerve and sensory nerve, collectively referred to as CMT and its related diseases. CMT can be divided into demyelinating type (CMT1), axonal type (CMT2) and intermediate type. There are more than 80 kinds of genes discovered so far, and genetic diagnosis plays a vital role in the treatment of peroneal muscular atrophy and genetic counseling.

[Purpose]

1. To clarify the gene lineage distribution of CMT genes in CMT patients in my country, draw a frequency map of CMT gene distribution, and assist in determining the genetic diagnosis strategy of CMT diseases;
2. Discover new mutations and newly published types of known genes, and perform gene-phenotype correlation analysis
3. Perform whole-exome sequencing on some families that have not been clearly diagnosed to find new pathogenic genes or related genes of CMT, so as to enrich the genetic and clinical types of CMT.

[Design] This is a cross-sectional study. All patients will be collected for clinical and electrophysiological data. Patients and families who meet the enrollment criteria will be tested for blood tests. The inspection strategies are as follows: (1) Use MLPA method for PMP22 gene Duplicate or deletion mutation check (charge); (2)) Use high-throughput sequencing method to detect the currently known gene panel (gene panel) (charge); (3) Check the process (1) and (2) Some patients and families whose disease-causing genes have not been detected by the inspection methods are tested by whole-exome sequencing (scientific research, free of charge).