A deletion of five nucleotides in the LICAM gene in a Japanese family with X-linked hydrocephalus

摘要

X-linked hydrocephalus (HSAS) is the most common form of inherited hydrocephalus characterized by hydrocephalus due to stenosis of the aqueduct of Sylvius, mental retardation, clasped thumbs, and spastic paraparesis. MASA syndrome (mental retardation, aphasia, shuffling gait and adducted thumbs) and SPG1 (X-linked complicated spastic paraplegia) are also X-linked disorders with overlapping clinical signs. Linkage analysis studies implicated the neural cell adhesion molecule L1 (LICAM) gene as a candidate gene for these X-linked disorders. This genetic study analyzes the LICAM gene in a Japanese family with members suffering from HSAS, and describes a deletion of five nucleotides in exon 8. Screening byBg1I digestion of polymerase chain reaction (PCR) products revealed that two siblings have the same mutation and a sister was identified as a heterozygous carrier. The 5 nucleotide deletion causes a shift of the reading frame and introduces a premature stop codon 72 nucleotides downstream, which might result in a truncated protein. The mutation identified herein is a novel L1 CAM mutation, which triggers hydrocephalus. We report a unique LlCAM mutation that causes HSAS: the first report of such a mutation in a Japanese family.