A DELETION OF 5 NUCLEOTIDES IN THE L1CAM GENE IN A JAPANESE FAMILY WITH X-LINKED HYDROCEPHALUS

X-linked hydrocephalus (HSAS) is the most common form of inherited hyd rocephalus characterized by hydrocephalus due to stenosis of the aqued uct of Sylvius, mental retardation, clasped thumbs, and spastic parapa resis. MASA syndrome (mental retardation, aphasia, shuffling gait and adducted thumbs) and SPG1 (X-linked complicated spastic paraplegia) ar e also X-linked disorders with overlapping clinical signs. Linkage ana lysis studies implicated the neural cell adhesion molecule L1 (L1CAM) gene as a candidate gene for these X-linked disorders. This genetic st udy analyzes the L1CAM gene in a Japanese family with members sufferin g from HSAS, and describes a deletion of five nucleotides in exon 8. S creening by Bg1I digestion of polymerase chain reaction (PCR) products revealed that two siblings have the same mutation and a sister was id entified as a heterozygous carrier. The 5 nucleotide deletion causes a shift of the reading frame and introduces a premature stop codon 72 n ucleotides downstream, which might result in a truncated protein. The mutation identified herein is a novel L1CAM mutation, which triggers h ydrocephalus, We report a unique LICAM mutation that causes HSAS: the first report of such a mutation in a Japanese family.