Identification of novel sequence variants in the neurofilament‐light gene in a Japanese population: analysis of Charcot‐Marie‐Tooth disease patients and normal individuals

Abstract  Mutations of the neurofilament‐light (NEFL/NF‐L) gene were examined in 124 unrelated Japanese patients with Charcot‐Marie‐Tooth disease (CMT) without known gene mutations, and 248 normal Japanese individuals. A new method, which can detect basepair mismatches with RNase cleavage on agarose gel electrophoresis, coupled with DNA sequencing, identified 8 novel sequence variations in the NF‐L gene. In these sequence variants, 5 variants were polymorphisms, including 3 single nucleotide polymorphisms (SNPs), and 3 other missense mutations (Pro22Thr, Asn97Ser and Ala148Val) were found in the patients with CMT phenotype. The variant alleles in the NF‐L gene could influence the developing process of CMT phenotype and also might cause CMT phenotype.

[1]  G. Sobue,et al.  A novel missense mutation in the early growth response 2 gene associated with late-onset Charcot–Marie–Tooth disease type 1 , 2001, Journal of the Neurological Sciences.

[2]  C. van Broeckhoven,et al.  Further evidence that neurofilament light chain gene mutations can cause Charcot‐Marie‐Tooth disease type 2E , 2001, Annals of neurology.

[3]  G. Sobue,et al.  An axonal form of Charcot-Marie-Tooth disease showing distinctive features in association with mutations in the peripheral myelin protein zero gene (Thr124Met or Asp75Val) , 2000, Journal of neurology, neurosurgery, and psychiatry.

[4]  G. Sobue,et al.  Mutations in the peripheral myelin protein zero and connexin32 genes detected by non‐isotopic RNase cleavage assay and their phenotypes in Japanese patients with Charcot‐Marie‐Tooth disease , 2000, Human mutation.

[5]  O. Evgrafov,et al.  A new variant of Charcot-Marie-Tooth disease type 2 is probably the result of a mutation in the neurofilament-light gene. , 2000, American journal of human genetics.

[6]  J. Lupski.  Axonal Charcot-Marie-Tooth disease and the neurofilament light gene (NF-L) , 2000, American journal of human genetics.

[7]  S. Komai,et al.  Site‐Specific Phosphorylation of Neurofilament‐L Is Mediated by Calcium/Calmodulin‐Dependent Protein Kinase II in the Apical Dendrites During Long‐Term Potentiation , 2000, Journal of neurochemistry.

[8]  A Al-Chalabi,et al.  Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis. , 1999, Human molecular genetics.

[9]  E. Fuchs,et al.  A structural scaffolding of intermediate filaments in health and disease. , 1998, Science.

[10]  G. Sobue,et al.  Locations of crossover breakpoints within the CMT1A-REP repeat in Japanese patients with CMT1A and HNPP , 1997, Human Genetics.

[11]  L. Bruijn,et al.  Sequence variants in human neurofilament proteins: Absence of linkage to familial amyotrophic lateral sclerosis , 1996, Annals of neurology.