Loss-of-function of EBP50 is a new cause of hereditary peripheral neuropathy: EBP50 functions in peripheral nerve system

Gyun Jee Song, Deepak Prasad Gupta, Md Habibur Rahman, Hwan Tae Park, Imad Al Ghouleh, Alessandro Bisello, Maan Gee Lee, Jae Yong Park, Hyun Ho Park, Jin Hyun Jun, Ki Wha Chung, Byung Ok Choi, Kyoungho Suk

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Finding causative genetic mutations is important in the diagnosis and treatment of hereditary peripheral neuropathies. This study was conducted to find new genes involved in the pathophysiology of hereditary peripheral neuropathy. We identified a new mutation in the EBP50 gene, which is co-segregated with neuropathic phenotypes, including motor and sensory deficit in a family with Charcot–Marie–Tooth disease. EBP50 is known to be important for the formation of microvilli in epithelial cells, and the discovery of this gene mutation allowed us to study the function of EBP50 in the nervous system. EBP50 was strongly expressed in the nodal and paranodal regions of sciatic nerve fibers, where Schwann cell microvilli contact the axolemma, and at the growth tips of primary Schwann cells. In addition, EBP50 expression was decreased in mouse models of peripheral neuropathy. Knockout mice were used to study EBP50 function in the peripheral nervous system. Interestingly motor function deficit and abnormal histology of nerve fibers were observed in EBP50+/− heterozygous mice at 12 months of age, but not 3 months. in vitro studies using Schwann cells showed that NRG1-induced AKT activation and migration were significantly reduced in cells overexpressing the I325V mutant of EBP50 or cells with knocked-down EBP50 expression. In conclusion, we show for the first time that loss of function due to EBP50 gene deficiency or mutation can cause peripheral neuropathy.

Original languageEnglish
Pages (from-to)1794-1809
Number of pages16
Issue number9
Publication statusPublished - 2020 Sept 1


  • Charcot–Marie–Tooth disease
  • EBP50
  • Schwann cells
  • ezrin–radixin–moesin-binding phosphoprotein
  • hereditary peripheral neuropathy
  • mutation

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience


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