Nature Genetics
7, 402 - 407 (1994)
doi:10.1038/ng0794-402
X−linked spastic paraplegia (SPG1), MASA syndrome and X−linked hydrocephalus result from mutations in the L1 geneMonique Jouet1, André Rosenthal2, Giles Armstrong1, John MacFarlane1, Roger Stevenson3, Joan Paterson4, Aïda Metzenberg5, Victor Ionasescu6, Karen Temple7
& Susan Kenwrick1, 8
1Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
2Institut für Molekulare Biotechnologie, Jena, Germany
3Greenwood Genetic Center, Greenwood, South Carolina, USA
4Duncan Guthrie Institute of Medical Genetics, Glasgow, UK
5Howard Hughes Medical Institute, University of California, San Francisco, USA
6Department of Pediatrics, University Hospital of Iowa, Iowa City, Iowa, USA
7Princess Anne Hospital, Southampton, UK
8Correspondence should be addressed to S.K. X−linked hydrocephalus, spastic paraplegia type I and MASA syndrome are related disorders with loci in subchromosomal region Xq28. We have previously shown that X−linked hydrocephalus is caused by mutations in the gene for neural cell adhesion molecule L1 (L1CAM), an axonal glycoprotein involved in neuronal migration and differentiation. Here we report mutations of the L1 gene in MASA syndrome and SPG1, in addition to 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 part of a clinical spectrum resulting from a heterogeneous group of mutations in the L1 gene.
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