title: Neurofilament light chain polypeptide gene mutations in Charcot-Marie-Tooth disease: nonsense mutation probably causes a recessive phenotype.
abstract: The neurofilament light chain polypeptide (NEFL) forms the major intermediate filament in neurons and axons. NEFL mutation is a cause of axonal or demyelinating forms of dominant Charcot-Marie-Tooth disease (CMT). We investigated NEFL in 223 Japanese CMT patients who were negative for PMP22, MPZ, GJB1, LITAF, EGR2, GDAP1, MTMR2 and PRX in the demyelinating form and negative for MFN2, MPZ, GJB1, HSP27, HSP22 and GARS in the axonal form. We detected four heterozygous missense mutations--Pro8Leu, Glu90Lys, Asn98Ser and Glu396Lys--in five unrelated patients and a homozygous nonsense mutation, Glu140Stop, in one other patient. All patients had mildly to moderately delayed nerve conduction velocities, possibly caused by a loss of large diameter fibers. This is the first report of a homozygous nonsense mutation of NEFL. Results of our study show that nonsense NEFL mutations probably cause a recessive phenotype, in contrast to missense mutations, which cause a dominant phenotype.
authors.affiliation: Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Abe
authors.forename: Chikahiko
authors.initials: C
authors.lastname: Numakura
authors.forename: Kayoko
authors.initials: K
authors.lastname: Saito
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Koide
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Oka
authors.forename: Akira
authors.initials: A
authors.lastname: Honma
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kishikawa
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hayasaka
mesh_terms: D000293:Adolescent; D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D016900:Neurofilament Proteins / Q000235:genetics*; D010641:Phenotype
chemical_list: D018389:Codon, Nonsense; D016900:Neurofilament Proteins; C044882:neurofilament protein L