5 NOVEL MUTATIONS IN THE L1CAM GENE IN FAMILIES WITH X-LINKED HYDROCEPHALUS

Five novel mutations have been identified in the gene encoding L1CAM, a neural cell adhesion protein, in families with X linked hydrocephalu s (XHC). Interestingly, all five mutations are in the evolutionarily h ighly conserved Ig-like domains of the protein. The two frameshift mut ations (52insC and 955delG) and the nonsense mutation (Trp276Ter) most probably result in functional null alleles and complete absence of L1 CAM at the cell surface. The two missense mutations (Tyr194Cys and Pro 240Leu) may considerably alter the structure of the L1CAM protein. The se data provide convincing evidence that XHC is genetically extremely heterogeneous.