M. Jouet et al., X-LINKED SPASTIC PARAPLEGIA (SPG1), MASA SYNDROME AND X-LINKED HYDROCEPHALUS RESULT FROM MUTATIONS IN THE L1 GENE, Nature genetics, 7(3), 1994, pp. 402-407
X-linked hydrocephalus, spastic paraplegia type I and MASA syndrome ar
e related disorders with loci in subchromosomal region Xq28. We have p
reviously shown that X-linked hydrocephalus is caused by mutations in
the gene for neural cell adhesion molecule L1 (L1CAM), an axonal glyco
protein involved in neuronal migration and differentiation. Here we re
port mutations of the L1 gene in MASA syndrome and SPG1, in addition t
o HSAS families. Two of the HSAS mutations would abolish cell surface
expression of L1 and represent the first functional null mutations in
this disorder. Our results indicate that these three syndromes form pa
rt of a clinical spectrum resulting from a heterogeneous group of muta
tions in the L1 gene.