Peripheral Myelin Protein 22 Gene Mutations in Charcot-Marie-Tooth Disease Type 1E Patients

Genes (Basel). 2022 Jul 8;13(7):1219. doi: 10.3390/genes13071219.


Duplication and deletion of the peripheral myelin protein 22 (PMP22) gene cause Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP), respectively, while point mutations or small insertions and deletions (indels) usually cause CMT type 1E (CMT1E) or HNPP. This study was performed to identify PMP22 mutations and to analyze the genotype-phenotype correlation in Korean CMT families. By the application of whole-exome sequencing (WES) and targeted gene panel sequencing (TS), we identified 14 pathogenic or likely pathogenic PMP22 mutations in 21 families out of 850 CMT families who were negative for 17p12 (PMP22) duplication. Most mutations were located in the well-conserved transmembrane domains. Of these, eight mutations were not reported in other populations. High frequencies of de novo mutations were observed, and the mutation sites of c.68C>G and c.215C>T were suggested as the mutational hotspots. Affected individuals showed an early onset-severe phenotype and late onset-mild phenotype, and more than 40% of the CMT1E patients showed hearing loss. Physical and electrophysiological symptoms of the CMT1E patients were more severely damaged than those of CMT1A while similar to CMT1B caused by MPZ mutations. Our results will be useful for the reference data of Korean CMT1E and the molecular diagnosis of CMT1 with or without hearing loss.

Keywords: Charcot-Marie-Tooth disease type 1E (CMT1E); Korean; PMP22; point mutation; whole-exome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthrogryposis
  • Charcot-Marie-Tooth Disease* / genetics
  • Deafness
  • Hereditary Sensory and Motor Neuropathy
  • Humans
  • Mutation
  • Myelin Proteins / genetics*


  • Myelin Proteins
  • PMP22 protein, human

Supplementary concepts

  • Charcot-Marie-Tooth Disease, Demyelinating, Type 1e
  • Charcot-Marie-Tooth disease, Type 1E
  • Tomaculous neuropathy

Grant support

This research was supported by grants from the National Research Foundation (2019R1A2C1087547, 2020M3H4A1A03084600 and 2021R1A4A2001389) and the Korean Health Technology R&D Project, Ministry of Health and Welfare (HI14C3484 and HI20C0039), Republic of Korea.