Communicated by Mark H. Paalman
Mutation in Brief
Article first published online: 31 MAR 2004
Copyright © 2004 Wiley-Liss, Inc.
Volume 23, Issue 5, page 526, May 2004
How to Cite
Hübner, C. A., Utermann, B., Tinschert, S., Krüger, G., Ressler, B., Steglich, C., Schinzel, A. and Gal, A. (2004), Intronic mutations in the L1CAM gene may cause X-linked hydrocephalus by aberrant splicing. Hum. Mutat., 23: 526. doi: 10.1002/humu.9242
Online Citation: Human Mutation, Mutation in Brief #713 (2004) Onlinehttp://www3.interscience.wiley.com/homepages/38515/pdf/mutation/713.pdf
- Issue published online: 31 MAR 2004
- Article first published online: 31 MAR 2004
- Manuscript Accepted: 19 FEB 2004
- Manuscript Received: 23 SEP 2003
- Cited By
- L1 disease;
- mutation analysis
L1 disease is a clinically heterogeneous X-chromosomal neurodevelopmental disorder that is frequently associated with mental retardation and congenital hydrocephalus in males. It is caused by mutations in L1CAM that encodes a multifunctional transmembrane neuronal cell adhesion molecule. We report our findings on 6 novel intronic L1CAM sequence variants (c.523+5G>A, c.1123+1G>A, c.1547-13delC, c.3323-17dupG, c.3457+3A>T, and c.3457+18C>T), and a recurrent one (c.523+12C>T). While the pathogenic potential of nucleotide changes within the evolutionarily well-conserved splice consensus sequence (c.523+5G>A, c.1123+1G>A, and c.3457+3A>T) is widely accepted, it is not always straight forward to assess the disease relevance of intronic mutations, if they lie outside the consensus. The c.523+12C>T variant co-segregated with X-linked hydrocephalus in two unrelated families. In the mutated allele, a preferentially used novel splice donor site is generated that results in a frame shift due to insertion of the first 10 bp of intron 5 in the mature mRNA, a largely truncated protein, and most likely a functional null allele. The c.1547-13delC mutation creates a new acceptor site resulting in the insertion of 4 additional amino acids at the end of the immunoglobulin like domain 5. In contrast, c.3323-17dupG and c.3457+18C>T seem to be non-pathogenic L1CAM variants. © 2004 Wiley-Liss, Inc.