Mutations in L1cam, a member of the immunoglobulin (Ig) superfamily that mediate cell-cell contacts through homo- and heterophilic interactions, are associated with several developmental abnormalities of the nervous system, including mental retardation, limb spasticity, hydrocephalus, and corpus callosum aplasia.
Mutations of the human L1CAM gene have been shown to cause neurodevelopmental disorders such as X-linked hydrocephalus, spastic paraplegia and mental retardation.
Mutations in the X-chromosomal gene (L1CAM) for cell adhesion molecule L1 are associated with a heterogeneous group of conditions that include agenesis of the corpus callosum, hydrocephalus, spastic paraplegia, adducted thumbs and mental retardation (L1-spectrum disease, CRASH or MASA syndrome).
The finding of a significant number of copy number polymorphisms in the genome in the normal population, means that assigning pathogenicity to deletions and duplications in patients with mental retardation can be difficult but has been identified for duplications of MECP2 and L1CAM.
The duplications in the four patients vary in size from 0.4 to 0.8 Mb and harbor several genes, which, for each duplication, include the MR-related L1CAM and MECP2 genes.
Mutations in L1CAM, the gene encoding the L1 neuronal cell adhesion molecule, lead to an X-linked trait characterized by one or more of the symptoms of hydrocephalus, adducted thumbs, agenesis or hypoplasia of corpus callosum, spastic paraplegia, and mental retardation (L1-disease).
The L1CAM gene, which is located in Xq28 and codes for a neuronal cell adhesion molecule, is involved in three distinct conditions: HSAS (hydrocephalus-stenosis of the aqueduct of Sylvius), MASA (mental retardation, aphasia, shuffling gait, adductus thumbs), and SPG1 (spastic paraplegia).
Mutations in the gene encoding the neuronal cell adhesion molecule L1 are responsible for several syndromes with clinical overlap, including X-linked hydrocephalus (XLH, HSAS), MASA (mental retardation, aphasias, shuffling gait, adducted thumbs) syndrome, complicated X-linked spastic paraplegia (SP 1), X-linked mental retardation-clasped thumb (MR-CT) syndrome, and some forms of X-linked agenesis of the corpus callosum (ACC).
Recently, studies in the usually disparate fields of human genetics and developmental neurobiology have converged to reveal that some types of human mental retardation and brain malformations are due to mutations that affect the neural cell adhesion molecule L1.