Clinical and Molecular Genetics of Inherited Hydrocephalus*

ABSTRACTCongenital hydrocephalus has a broad spectrum of etiology and has not been elucidated in terms of pathogenesis or mechanism of hydrocephalus. Recent advance of molecular genetics disclosed the genetic defects of X‐linked hydrocephalus (HSAS), MASA syndrome and X‐linked spastic paraplegia (SPGI), characterized by mutations in LICAM, a gene coding for a neural cell adhension molecule. Meanwhile, genetic heterogeneity in X‐linked hydrocephalus has been pointed out; linkage to markers within Xq27.3. We reviewed inherited hydrocephalus and chromosomal aberrations with hydrocephalus because fibroblasts from patients with these disorders may be useful for a molecular genetic approach to inherited hydrocephalus. Animal models of congenital hydrocephalus are also very important for a comparative mapping analysis between mice and human. We have tried to clone a candidate gene of hydrocephalus using fibroblasts which show a de nove chromosomal aberration [t(4;16)(q35;q22.1)], because the synteny conservation locus for mouse hydrocephalus‐3 (hy‐3) gene is suggested to be located in the long arm of human chromosome 16. A rearranged band of 1.2 Mb was detected by Pulse‐Field Gel Electrophoresis (PFGE) with Not I digestion using the calretinin probe. It may exist within 1.2 Mb distal apart from calretinin gene. Further analysis is carried out in order to clone this candidate gene of congenital hydrocephalus.