Mutations in the L1CAM gene produce a phenotype characterised by X linked hydrocephalus, mental retardation, spastic paraplegia, adducted thumbs, and agenesis of the corpus callosum.
Mutations in the gene for neural cell adhesion molecule L1 are responsible for the highly variable phenotype found in families with X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type I.
If this were indeed the case, our data suggest that the XHC in this family is not due to a mutation of the L1CAM gene, i.e., that, in addition to the extreme allelic heterogeneity of XHC, a non-allelic form of genetic heterogeneity may also exist in this trait.
Although the disease phenotypes of this patient may well be independent, the alternative explanation that L1CAM mutations may contribute to both phenotypes cannot be excluded in view of an earlier report on another patient with both X linked hydrocephalus and HSCR.
We sequenced the coding region of the L1CAM gene of patients from two different families with X-linked hydrocephalus and found a novel mutation at nucleotide residue 1963 in one family.
Recently, we have shown that mutations in the gene encoding L1 are responsible for three related disorders; X-linked hydrocephalus, MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs) syndrome, and spastic paraplegia type I (SPG1).
The inter- and intrafamilial variability in families with an L1 mutation is very wide, and patients with HSAS, MASA, SP1 and ACC can be present within the same family.
Since it has been shown that X-linked hydrocephalus can be caused by mutations in L1CAM, a neuronal cell adhesion molecule, we performed an L1CAM mutation analysis in eight unrelated patients with MASA syndrome.