Human Molecular Genetics Advance Access originally published online on July 28, 2004
Human Molecular Genetics 2004 13(19):2207-2220; doi:10.1093/hmg/ddh236
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Human Molecular Genetics, Vol. 13, No. 19 © Oxford University Press 2004; all rights reserved
Phenotypic analysis of neurofilament light gene mutations linked to Charcot-Marie-Tooth disease in cell culture models
Department of Pathology and Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA
Received May 5, 2004; Accepted July 12, 2004
Mutations in the neurofilament light (NFL) gene cause Charcot-Marie-Tooth (CMT) disease. There is a wide range of clinical presentations in CMT patients harboring NFL mutations, with patients classified as CMT2E or CMT1F. In this study, we analyzed the effects of five NFL mutations on the assembly and intracellular distribution of intermediate filaments (IFs), and compared the results with those obtained previously for other NFL mutations. Although all NFL mutants affected the formation of IF networks, our data show differential effects on the assembly of IFs depending on the exact nature of the mutation. 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. These results show that defects in the assembly and transport of NFs are common to all NFL mutants studied thus far, but the exact nature of the defect appears to be correlated with each mutant genotype.
* To whom correspondence should be addressed. Tel: +1 2123054078; Fax: +1 2123055498; Email: rkl2{at}columbia.edu
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