title: New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome.
abstract: The neural cell-adhesion molecule L1 is involved in intercellular recognition and neuronal migration in the CNS. 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). These three disorders represent a clinical spectrum that varies not only between families but sometimes also within families. To date, 14 independent L1 mutations have been reported and shown to be disease causing. Here we report nine novel L1 mutations in X-linked hydrocephalus and MASA-syndrome families, including the first examples of mutations affecting the fibronectin type III domains of the molecule. They are discussed in relation both to phenotypes and to the insights that they provide into L1 function.
authors.affiliation: University of Cambridge Department of Medicine, Addenbrooke's Hospital, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Jouet
authors.forename: A
authors.initials: A
authors.lastname: Moncla
authors.forename: J
authors.initials: J
authors.lastname: Paterson
authors.forename: C
authors.initials: C
authors.lastname: McKeown
authors.forename: A
authors.initials: A
authors.lastname: Fryer
authors.forename: N
authors.initials: N
authors.lastname: Carpenter
authors.forename: E
authors.initials: E
authors.lastname: Holmberg
authors.forename: C
authors.initials: C
authors.lastname: Wadelius
authors.forename: S
authors.initials: S
authors.lastname: Kenwrick
mesh_terms: D000015:Abnormalities, Multiple / Q000209:etiology* / Q000235:genetics; D001483:Base Sequence; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D017124:Conserved Sequence; D005260:Female; D005353:Fibronectins / Q000235:genetics; D008040:Genetic Linkage; D005820:Genetic Testing; D006801:Humans; D006849:Hydrocephalus / Q000209:etiology* / Q000235:genetics; D039841:Leukocyte L1 Antigen Complex; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011487:Protein Conformation; D017422:Sequence Analysis, DNA; D012729:Sex Chromosome Aberrations / Q000209:etiology / Q000235:genetics; D014960:X Chromosome / Q000235:genetics*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D005353:Fibronectins; D039841:Leukocyte L1 Antigen Complex