Mutations in the gene encoding
neural cell adhesion molecule L1 (
L1CAM) are involved in X-linked hydrocephalus (HSAS,
hydrocephalus due to
stenosis of the aqueduct of Sylvius),
MASA syndrome (
mental retardation, aphasia, shuffling gait, and adducted thumbs), and
spastic paraplegia type 1. We examined the
L1CAM mutation in a Japanese family with HSAS for the purpose of
DNA-based genetic counseling. The proband was a 9-year-old boy who had a 1-bp deletion in exon 22 of the
L1CAM gene. This resulted in a shift of the reading frame, and introduction of a
premature stop codon. Translation of this
mRNA will create a truncated
protein without the transmembrane domain, which cannot be expressed on the cell surface. Magnetic resonance images (MRI) revealed markedly enlarged lateral ventricles, hypoplastic white matter, thin cortical mantle, agenesis of the corpus callosum and septum pellucidum, and a fused thalamus. These findings represented impaired
L1CAM function during development of the nervous system with resultant adhesion between neurons, neurites outgrowth and
fasciculation, and neural cell migration. Screening by Apa I digestion of polymerase chain reaction (PCR) products identified the mother and the younger sister as heterozygous carriers. The carriers were asymptomatic. The father and the other sister did not have the mutation. The identification of
L1CAM mutation in families with HSAS will give them the opportunity for
DNA-based counseling and prenatal diagnosis.