Recently a set of mutations in the neurofilament light gene (NF-L) was reported in patients suffering from axonal and demyelinating forms of Charcot-Marie-Tooth disease (CMT1 and CMT2).
This study demonstrated normal function of the low-molecular-weight neurofilament protein (NFL) in mitochondrial dynamics and disruption in Charcot-Marie-Tooth disease (CMT) due to mutations in the Nefl gene.
We identified a similar aggregation-inducing mechanism in NEFL (neurofilament light) and FUS (fused in sarcoma), in which mutations are known to cause aggregation in Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis, respectively.
The novel neurofilament light (NEFL) mutation Glu397Lys is associated with a clinically and morphologically heterogeneous type of Charcot-Marie-Tooth neuropathy.
We examined CMT1A duplication of 17p11.2-p12, mutations of PMP22, MPZ (P0), GJB1 (Cx32), EGR2 and NEFL genes in 57 Korean families with patients diagnosed as having Charcot-Marie-Tooth (CMT) disease.
We conclude that the NEFLN98S mutation is associated with a DI-CMT phenotype characterized by early-onset sensorimotor neuropathy delaying motor milestones, which may evolve into a severe and complex clinical picture including cerebellar ataxia.
We performed a mutational analysis of NEFL in a series of 177 index cases with CMT and without mutations in the genes for peripheral myelin protein zero (MPZ), peripheral myelin protein 22 (PMP22) and connexin 32 (GJB1); the motor nerve conduction velocity (MNCV) at the median nerve was below 38 m/s in 76 cases and above 38 m/s in 101.
Defective transport of the mutant NFL subunits was observed for all the CMT-linked NFL mutations, but the characteristics of this defect also depended on the specific mutation.
We demonstrated that the Charcot-Marie-Tooth-linked neurofilament light mutations: (i) affect the axonal transport of mutant neurofilaments; (ii) have a dominant-negative effect on the transport of wild-type neurofilaments; (iii) affect the transport of mitochondria and the anterograde axonal transport marker human amyloid precursor protein; (iv) result in alterations of retrograde axonal transport and (v) cause fragmentation of the Golgi apparatus.
To analyse and describe the clinical and genetic spectrum of Charcot-Marie-Tooth disease (CMT) caused by mutations in the neurofilament light polypeptide gene (<i>NEFL</i>).