Five novel mutations in the L1CAM gene in families with X linked hydrocephalus.

• DOI: 10.1136/jmg.33.2.103
• Publication Date: 2008-11-10T20:37:21Z
• Authors: S M Gu; U Orth; A Veske; H Enders; K Klunder; M Schlosser; W Engel; E Schwinger; A Gal
• Keywords: Male; 0303 health sciences; Base Sequence; DNA Mutational Analysis; Molecular Sequence Data; Infant, Newborn; Pedigree; Fetal Diseases; 03 medical and health sciences; Genes; Intellectual Disability; Mutation; Humans; Abnormalities, Multiple; Female; Amino Acid Sequence; Agenesis of Corpus Callosum; Frameshift Mutation; Leukocyte L1 Antigen Complex; Neural Cell Adhesion Molecules; Alleles; Hydrocephalus

Five novel mutations have been identified in the gene encoding L1CAM, a neural cell adhesion protein, in families with X linked hydrocephalus (XHC). Interestingly, all five mutations are in the evolutionarily highly conserved Ig-like domains of the protein. The two frameshift mutations (52insC and 955delG) and the nonsense mutation (Trp276Ter) most probably result in functional null alleles and complete absence of L1CAM at the cell surface. The two missense mutations (Tyr194Cys and Pro240Leu) may considerably alter the structure of the L1CAM protein. These data provide convincing evidence that XHC is genetically extremely heterogeneous.