X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene

Nat Genet. 1994 Jul;7(3):402-7. doi: 10.1038/ng0794-402.


X-linked hydrocephalus, spastic paraplegia type I and MASA syndrome are related disorders with loci in subchromosomal region Xq28. We have previously shown that X-linked hydrocephalus is caused by mutations in the gene for neural cell adhesion molecule L1 (L1CAM), an axonal glycoprotein involved in neuronal migration and differentiation. Here we report mutations of the L1 gene in MASA syndrome and SPG1, in addition to HSAS families. Two of the HSAS mutations would abolish cell surface expression of L1 and represent the first functional null mutations in this disorder. Our results indicate that these three syndromes from part of a clinical spectrum resulting from a heterogeneous group of mutations in the L1 gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aphasia / genetics*
  • Base Sequence
  • Cell Adhesion Molecules, Neuronal / chemistry
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Cell Adhesion Molecules, Neuronal / physiology
  • Cell Movement
  • Chromosome Mapping
  • DNA Mutational Analysis
  • Female
  • Gait
  • Genes*
  • Humans
  • Hydrocephalus / genetics*
  • Intellectual Disability / genetics*
  • Leukocyte L1 Antigen Complex
  • Male
  • Models, Molecular
  • Molecular Sequence Data
  • Neurons / pathology
  • Paraplegia / genetics*
  • Phenotype
  • Point Mutation
  • Polymorphism, Single-Stranded Conformational
  • Protein Conformation
  • Pyramidal Tracts / pathology
  • Sequence Deletion
  • Syndrome
  • Thumb / abnormalities
  • X Chromosome*


  • Cell Adhesion Molecules, Neuronal
  • Leukocyte L1 Antigen Complex