Abnormal corticospinal function but normal axonal guidance in human L1CAM mutations

C. B. Dobson, F. Villagra, G. J. Clowry, M. Smith, S. Kenwrick, D. Donnai, S. Miller, J. A. Eyre

Research output: Contribution to journalArticlepeer-review

29 Citations (SciVal)


L1 cell adhesion molecule (L1CAM) gene mutations are associated with X-linked 'recessive' neurological syndromes characterized by spasticity of the legs. L1CAM knock-out mice show hypoplasia of the corticospinal tract and failure of corticospinal axonal decussation and projection beyond the cervical spinal cord. The aim of this study was to determine if similar neuropathology underlies the spastic diplegia of males hemizygous for L1CAM mutations. Studies were performed on eight carrier females and 10 hemizygous males. Transcranial magnetic stimulation excited the corticospinal tract and responses were recorded in biceps brachii and quadriceps femoris. In contralateral biceps and quadriceps the responses had high thresholds and delayed onset compared with normal subjects. Ipsilateral responses in biceps were smaller, with higher thresholds and delayed onsets relative to contralateral responses. Subthreshold corticospinal conditioning of the stretch reflex of biceps and quadriceps was abnormal in both hemizygous males and carrier females suggesting there may also be a reduced projection to inhibitory interneurones. Histological examination of post-mortem material from a 2-week-old male with an L1CAM mutation revealed normal corticospinal decussation and axonal projections to lumbar spinal segments. These data support a role for L1CAM in corticospinal tract development in hemizygous males and 'carrier' females, but do not support a critical role for L1CAM in corticospinal axonal guidance.

Original languageEnglish
Pages (from-to)2393-2406
Number of pages14
Issue number12
Publication statusPublished - Dec 2001


  • Adolescent
  • Adult
  • Axons
  • Child
  • Child, Preschool
  • Electric Stimulation
  • Female
  • GAP-43 Protein
  • Genetic Linkage
  • Heterozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Leukocyte L1 Antigen Complex
  • Magnetics
  • Male
  • Membrane Glycoproteins
  • Middle Aged
  • Motor Cortex
  • Motor Skills
  • Muscle, Skeletal
  • Mutation
  • Neural Cell Adhesion Molecules
  • Pyramidal Tracts
  • Reflex, Stretch
  • X Chromosome
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Ipsilateral
  • L1CAM
  • Corticospinal
  • Man
  • TMS


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