X-linked hydrocephalus: a novel missense mutation in the L1CAM gene.

X-linked hydrocephalus is associated with mutations in the L1 neuronal cell adhesion molecule gene. L1 protein plays a key role in neurite outgrowth, axonal guidance, and pathfinding during the development of the nervous system. A male is described with X-linked hydrocephalus who had multiple small gyri, hypoplasia of the white matter, agenesis of the corpus callosum, and lack of cleavage of the thalami. Scanning the L1 neuronal cell adhesion molecule gene in Xq28 revealed a novel missense mutation: transition of a guanine to cytosine at position 1,243, which led to conversion of alanine to proline at position 415 in the Ig 4 domain of the L1 protein. It is likely that the X-linked hydrocephalus and cerebral dysgenesis are a result of the abnormal structure and function of the mutant L1 protein.