L1CAM MUTATION IN A JAPANESE FAMILY WITH X-LINKED HYDROCEPHALUS - A STUDY FOR GENETIC-COUNSELING

Mutations in the gene encoding neural cell adhesion molecule L1 (L1CAM ) are involved in X-linked hydrocephalus (HSAS, hydrocephalus due to s tenosis of the aqueduct of Sylvius), MASA syndrome (mental retardation , aphasia, shuffling gait, and adducted thumbs), and spastic paraplegi a type 1. We examined the L1CAM mutation in a Japanese family with HSA S 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. Th is resulted in a shift of the reading frame, and introduction of a pre mature stop codon. Translation of this mRNA will create a truncated pr otein without the transmembrane domain, which cannot be expressed on t he cell surface. Magnetic resonance images (MRI) revealed markedly enl arged lateral ventricles, hypoplastic white matter, thin cortical mant le, agenesis of the corpus callosum and septum pellucidum, and a fused thalamus. These findings represented impaired L1CAM function during d evelopment of the nervous system with resultant adhesion between neuro ns, neurites outgrowth and fasciculation, and neural cell migration. S creening by Apa I digestion of polymerase chain reaction (PCR) product s identified the mother and the younger sister as heterozygous carrier s. The carriers were asymptomatic. The father and the other sister did not have the mutation. The identification of L1CAM mutation in famili es with HSAS will give them the opportunity for DNA-based counseling a nd prenatal diagnosis. (C) 1997 Elsevier Science B.V.