title: Nine novel L1 CAM mutations in families with X-linked hydrocephalus.
abstract: 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. To date, 32 different mutations have been observed, the majority being unique to individual families. Here, we report nine novel mutations in L1 in 10 X-linked hydrocephalus families. Four mutations truncate the L1 protein and eliminate cell surface expression, and two would produce abnormal L1 through alteration of RNA processing. A further two of these mutations are small in-frame deletions that have occurred through a mechanism involving tandem repeated sequences. Together with a single missense mutation, these latter examples contribute to the growing number of existing mutations that affect short regions of the L1 protein that may have particular functional significance.
authors.affiliation: University of Cambridge Department of Medicine, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: MacFarlane
authors.forename: J S
authors.initials: JS
authors.lastname: Du
authors.forename: M E
authors.initials: ME
authors.lastname: Pepys
authors.forename: S
authors.initials: S
authors.lastname: Ramsden
authors.forename: D
authors.initials: D
authors.lastname: Donnai
authors.forename: R
authors.initials: R
authors.lastname: Charlton
authors.forename: C
authors.initials: C
authors.lastname: Garrett
authors.forename: J
authors.initials: J
authors.lastname: Tolmie
authors.forename: J R
authors.initials: JR
authors.lastname: Yates
authors.forename: C
authors.initials: C
authors.lastname: Berry
authors.forename: D
authors.initials: D
authors.lastname: Goudie
authors.forename: A
authors.initials: A
authors.lastname: Moncla
authors.forename: P
authors.initials: P
authors.lastname: Lunt
authors.forename: S
authors.initials: S
authors.lastname: Hodgson
authors.forename: M
authors.initials: M
authors.lastname: Jouet
authors.forename: S
authors.initials: S
authors.lastname: Kenwrick
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D006849:Hydrocephalus / Q000235:genetics*; D007438:Introns; D039841:Leukocyte L1 Antigen Complex; D008297:Male; D009154:Mutation; D019006:Neural Cell Adhesion Molecules / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017384:Sequence Deletion; D014960:X Chromosome / Q000235:genetics
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D039841:Leukocyte L1 Antigen Complex; D019006:Neural Cell Adhesion Molecules