title: The neurofilament light chain gene (NEFL) mutation Pro22Ser can be associated with mixed axonal and demyelinating neuropathy.
abstract: We report the detailed clinical, electrophysiological and molecular analysis of a patient with Charcot-Marie-Tooth (CMT) disease. DNA sequencing of the coding sequences of the neurofilament light chain polypeptide (NEFL) gene revealed a c.64C>T heterozygous, missense mutation resulting in a Pro22Ser amino acid substitution. Clinical and electrophysiological studies revealed a mixed axonal and demyelinating neuropathy, with widespread demyelination involving both proximal and distal nerve segments. Mutations at this site in the NEFL gene have been previously linked to an axonal neuropathy or distal nerve demyelination. Our results emphasize the complexity of genotype-phenotype correlations in CMT and underline the possible importance of host factors and gene interactions in the development of clinical phenotypes.
authors.affiliation: Department of Neurology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA. sbhagavati@downstate.edu
authors.forename: Satyakam
authors.initials: S
authors.lastname: Bhagavati
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Maccabee
authors.forename: Weimin
authors.initials: W
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004568:Electrodiagnosis; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009431:Neural Conduction / Q000235:genetics; D016900:Neurofilament Proteins / Q000235:genetics*; D010525:Peripheral Nerves / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D011392:Proline / Q000235:genetics; D012694:Serine / Q000235:genetics
chemical_list: D005819:Genetic Markers; D016900:Neurofilament Proteins; C044882:neurofilament protein L; D012694:Serine; D011392:Proline