DISCORDANT SEGREGATION OF XQ28 MARKERS AND A MUTATION IN THE L1 GENE IN A FAMILY WITH X-LINKED HYDROCEPHALUS

X linked recessive hydrocephalus is the most common hereditary form of hydrocephalus. Genetic analysis indicates that the majority of cases are caused by mutations in a single gene in Xq28, recently identified as the gene for neural cell adhesion molecule L1. Genetic heterogeneit y for this disorder was suggested following the description of a singl e large pedigree where X linked hydrocephalus showed lack of linkage t o Xq28 markers flanking the L1 gene. Mutation analysis in this family shows a single base pair deletion within the coding sequence of the L1 gene that would result in truncation of the mature protein. The natur e of the mutation and its segregation with the disease through the ped igree indicate that it is the cause of X linked hydrocephalus in this family. These results are at odds with data obtained through segregati on of alleles for markers flanking the L1 gene. Somatic and germline m osaicism is the most plausible explanation for these data, which also provide further evidence for genetic homogeneity of X linked hydroceph alus.