9 NOVEL L1 CAM MUTATIONS IN FAMILIES WITH X-LINKED HYDROCEPHALUS

Mutations in the gene for neural cell adhesion molecule L1 are respons ible for the highly variable phenotype found in families with X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type I. To date, 32 different mutations have been observed, the majority being unique to individual families, Here, we report nine novel mutations in L1 in 10 X-linked hydrocephalus families. Four mutations truncate the L1 pro tein and eliminate cell surface expression, and two would produce abno rmal L1 through alteration of RNA processing. A further two of these m utations are small in frame deletions that have occurred through a mec hanism involving tandem repeated sequences. Together with a single mis sense mutation, these latter examples contribute to the growing number of existing mutations that affect short regions of the L1 protein tha t may have particular functional significance. (C) 1997 Wiley Liss, In c.