Neurofilament light chain (NEFL) 유전자 돌연변이 CMT 환자들의 전기생리학적 특성

Abstract

Objectives: Charcot-Marie-Tooth (CMT) disease is the most common form of hereditary motor and sensory neuropathy. Several genes were recently identified to cause autosomal dominant CMT2 including neurofilament light chain(NEFL) gene. NEFL encodes a 62kDa structural protein, which is one of the most abundant cytoskeletal components of neural cells. CMT with NEFL gene was recently known and there was controversies about the pathogical and electophysiological changes in this disease. Therefore, we investigated to find the pathological and electrophysiological characteristics in Korean CMT patients with NEFL mutation.

Methods: Mutations of the NEFL gene were examed in 125 unrelated Korean families diagnosed as having CMT disease, and 105 normal individuals. Nerve conduction studies were carried out all study populations.

Results: Three pathogenic mutations (Pro22Arg, Leu334Pro, Glu397Lys) were found in three families (FC#7, 21, 99), respectively. Electrophyiologically, FC#21 patient represented axonal neuropathy (CMT2E), and the others showed demyelinating neuropathy (CMT1). In patient with Leu334Pro mutation, the results of follow-up nerve conduction studies showed very slow disease progress, and pathological findings displayed small loss of large myelinated fibers.

Conclusion: NEFL mutations cause both demyelinating and axonal neuropathies. Therefore, analysis of the NEFL gene should not be restricted to pure axonal neuropathy.